Artificial Butter Flavoring

Chemical Information Review Document

for

Artificial Butter Flavoring and Constituents

Diacetyl [CAS No 431-03-8] and Acetoin [CAS No 513-86-0]

Supporting Nomination for Toxicological Evaluation by the National Toxicology Program

January 2007

Prepared by Integrated Laboratory Systems Inc

Research Triangle Park NC Under Contract No N01-ES-35515

Prepared for National Toxicology Program

National Institute of Environmental Health Sciences National Institutes of Health

US Department of Health and Human Services Research Triangle Park NC

httpntpniehsnihgov

Abstract

Artificial butter flavoring and two important constituents diacetyl and acetoin were nominated by the United Food and Commercial Workers International Union for long-term testing via inhalation for respiratory and other toxicity and for cancer-causing properties There is growing concern that workers in the microwave popcorn manufacturing industry may be at risk of developing the lung disease bronchiolitis obliterans from exposure to vapors from artificial butter flavoring The first case of bronchiolitis obliterans in a popcorn manufacturing worker was reported in 2000 in Missouri Since then several devastating outbreaks of severe and even fatal lung disease including bronchiolitis obliterans have been documented among workers in microwave popcorn manufacturing plants who have been exposed to the vapors of butter flavoring To date limited toxicological studies are available for artificial butter flavoring and its constituents Inhalation studies in male rats showed that exposure to vapors from artificial butter flavoring caused necrosis of nasal and airway epithelium Necrotizing bronchitis was observed in the lung and necrosuppurative rhinitis and inflammation were seen at all nasal levels An inhalation study with diacetyl also produced significant necrosis of nasal epithelium and significant necrosis of tracheal epithelium in male rats However no significant effects in the lung were reported In another inhalation study necropsy revealed general congestion focal hyperemia of the lungs atelectasis and bloody edema of the lungs bronchial edema and intensified hydrothorax in rats that did not survive a four hour treatment with diacetyl Histopathological examination showed emphysema hyperemia of the lungs peripheral or centrilobular swelling of hepatocytes and necrosis in the proximal tubules of the kidney In rats [14C]-diacetyl given by intragastric gavage was rapidly metabolized and excreted primarily as carbon dioxide in the breath and in urine Metabolism of acetoin in vivo was mainly by oxidation at low concentrations and by reduction to 23-butanediol at higher concentrations Diacetyl was not a reproductive or teratological toxicant in studies with pregnant mice rats or hamsters Intraperitoneal injections of diacetyl or acetoin did not induce tumors in mice Diacetyl but not acetoin was mutagenic in some strains of bacteria It was negative in a micronucleus test but induced sister chromatid exchanges in Chinese hamster ovary AUXB1 cells and unscheduled DNA synthesis in various organs of laboratory animals Diacetyl exhibited activating and deactivating effects on several enzymes and metabolic processes It has been postulated that oxidative stress may play a role in diacetyl-induced lung damage

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Executive Summary

Basis for Nomination Artificial butter flavoring and two important constituents diacetyl and acetoin were nominated by the United Food and Commercial Workers International Union (UFCW) for long-term testing via inhalation for respiratory and other toxicity and for cancer-causing properties After the first incidence of bronchiolitis obliterans associated with microwave popcorn manufacturing in Jasper MO was reported in 2000 several devastating outbreaks of severe and even fatal lung disease including bronchiolitis obliterans have been documented among workers in other microwave popcorn plants who had been exposed to the vapors of butter flavoring These outbreaks have been reported in the scientific literature and the popular press Since butter flavoring mixtures consist of more than 100 different chemicals the most prominent being diacetyl and acetoin the UFCW also recommends that the flavoring mixture as a whole be tested and that the National Toxicology Program (NTP) explore the effects of compounds with chemical and physical properties similar to diacetyl and acetoin

Nontoxicological Data Diacetyl is naturally found in foods and is also used as a synthetic flavoring agent and an aroma carrier in foods including butter caramel vinegar dairy products and coffee Acetoin is used as a fragrance carrier and in the preparation of flavors and essences it is found in many of the same foodstuffs as diacetyl (eg butter corn wine and cocoa) In the United States diacetyl and acetoin are regulated by the Food and Drug Administration as substances directly added to human food and are generally recognized as safe Both compounds can be detected using gas chromatography usually coupled with flame ionization detection Diacetyl is available form several US suppliers and is produced in different ways including converting methyl ethyl ketone to an isonitroso compound followed by hydrolyzation with hydrochloric acid or by oxidation of 2-butanone over a copper catalyst Diacetyl is also a product of fermentation of glucose via methylacetylcarbinol and of lactic acid bacteria activity during the production of beer Acetoin is prepared from diacetyl by partial reduction with zinc and acid It is also produced by the action of sorbose bacteria or Mycoderma aceti on 23-butanediol or by the action of fungi on sugar cane juice It is a by-product of fermentation and preparation of cream for churning Diacetyl has been identified in aroma components of tobacco smoke and in several plants It photodegrades quickly in the atmosphere and is not likely to absorb significantly in soil or sediment or to bioconcentrate in fish Acetoin gradually oxidizes to diacetyl in air and forms a solid dimer on standing or treatment with granulated zinc It has high mobility if released to soil and is not expected to absorb to suspended solids or sediments or to undergo direct photolysis Like diacetyl it has a low potential for bioconcentration in aquatic organisms

Human Data Diacetyl and acetoin are formed endogenously in humans from decarboxylation of pyruvate They are important volatile organic compounds (VOCs) emitted from butter flavoring and are of concern to workers in the microwave popcorn production industry Case reports of severe bronchiolitis obliterans syndrome in eight former workers at a Missouri microwave popcorn plant (Gilster-Mary Lee Corporation) sparked public interest in May 2000 NIOSH reported that workers from three other microwave popcorn plants had been exposed to diacetyl and other VOCs form butter flavoring mixtures and had developed occupational lung disease at least three deaths were reported among these individuals Bronchiolitis obliterans has therefore been called popcorn workers lung or popcorn packers workers lung Of the eight workers at the Missouri plant four worked in the plants production area (included a mixing room) and four worked in the packaging areas Workers in these sections were exposed to 800x and 15x the mean atmospheric concentration of diacetyl respectively compared to office warehouse and outside areas Workers in the production areas also had significantly higher rates of shortness of breath on exertion breathing problems a combination of respiratory symptoms unusual fatigue other systemic symptoms and rashes or other skin problems As cumulative exposure to diacetyl increased the

ii

incidence of airway obstruction increased The data suggested diacetyl as a cause of respiratory disease or a marker of the causative exposure However workers in the production areas were also exposed to the highest concentrations of ketones other VOCs and respirable dust Bronchiolitis obliterans has also been reported in workers of other industries (baking industry flavoring manufacturing plants and snack food manufacturer using flavorings or spices)

Workers exposed to butter flavoring vapors have also reported eye (chemical burns) skin and nasal irritations Patch testing and maximization testing with diacetyl produced no irritation or sensitization respectively in volunteers Tests with acetoin also resulted in no irritation or sensitization reactions

Toxicological Data No short-termsubchronic or chronic inhalation studies were available for artificial butter flavorings diacetyl or acetoin Additionally data regarding initiationpromotion anticarcinogenicity and immunotoxicity were not found

Chemical Disposition Metabolism and Toxicokinetics Metabolic interconversion between diacetyl acetoin and 23-butanediol has been observed using rat liver extracts

When administered to male Fischer 344 rats via intragastric gavage a single dose of radiolabeled [14C]-diacetyl (158 158 or 158 mgkg [00184 0184 or 184 mmolkg]) resulted in excretion of 820 727 and 543 of the administered doses respectively as carbon dioxide at 72 hours In urine the excreted amounts were 686 157 and 341 respectively At all tested levels total excretion of radioactivity in urine feces and expired breath accounted for 86-87 of the dose recovered within 24 hours In normal rat liver mitochondria diacetyl uncoupled oxidative phosphorylation totally eliminated respiratory control with substrates and partially eliminated it with succinate

Metabolism of acetoin in vivo is mainly by oxidation at low concentrations and by reduction to 23-butanediol at high concentrations When acetoin (doses not provided) was ip injected into albino rats 12C-carbon dioxide was found in expired air (average of 15 during 12 hours) When acetoin was administered orally or subcutaneously to rats no diacetyl and very little acetoin were detected in the urine 23-butanediol was the major excretion product In rabbits orally given acetoin and in rabbit liver homogenate incubated with acetoin acetylation was increased In male guinea pigs acetoin was an intermediary metabolite in the reduction of methyl ethyl ketone to 23-butanediol In rat and rabbit liver extracts gt95 of radiolabeled [23-14C]-acetoin was detected as a mixture of 23-butanediol stereoisomers

Acute Toxicity The LC50 value for diacetyl in rats was reported between 225 and 52 mgL (639 and 1477 ppm) for a four-hour period Diacetyl was a severe skin and eye irritant in rabbits Acetoin was a moderate irritant on intact and abraded skin of rabbits an LD50 value gt5000 mgkg (5675 mmolkg) was calculated

Male rats exposed to vapors from artificial butter flavoring (average diacetyl concentrations 203 285 352 [constant] or 371 [pulsed] ppm range 72-940 ppm) for six hours exhibited necrosis of nasal and airway epithelium At levels of 285-371 ppm diacetyl necrotizing bronchitis was observed in the lung at 203-371 ppm diacetyl necrosuppurative rhinitis and inflammation were seen at all nasal levels

Inhalation of diacetyl (99 198 or 295 ppm [349 697 or 1039 mgm3]) for six hours also produced significant necrosis of nasal epithelium at ge198 ppm and significant necrosis of tracheal epithelium at the high dose in male rats No significant effects in the lung were reported When tested in male and female Wistar rats inhalation of diacetyl FCC (225 52 and 239 mgL [6390 1477 or 6788 ppm]) for four

iii

hours resulted in deaths at the mid and high doses Necropsy showed general congestion in dead rats focal hyperemia of the lungs and empty gastrointestinal tract in mid-dose animals and atelectasis and bloody edema of the lungs bronchial edema and intensified hydrothorax in high-dose rats Histopathological examination revealed moderate emphysema and focal hyperemia of the lungs as well as peripheral swelling of hepatocytes at the mid dose and widespread hyperemia of the lung necrosis in the proximal tubules of the kidney and centrilobular swelling of hepatocytes at the high dose

No acute inhalation studies for acetoin were available

SynergisticAntagonistic Effects When acetoin and ethanol were ip administered simultaneously in rats to cause loss of righting reflex and respiratory failure the concentrations of both chemicals were additive in blood

Cytotoxicity Diacetyl (0001 01 or 1 mM [0086 86 or 86 microgmL]) inhibited cell growth in ascites sarcoma cells by 37 at the mid dose and by 100 at the high dose

Reproductive and Teratological Effects When given via oral intubation to pregnant mice for ten days diacetyl (16 g starter distillatekg) had no effects on maternal or fetal survival or nidation and caused no statistically significant changes in the number of fetal abnormalities compared to controls Tests in hamsters and rats gave similar results

Carcinogenicity When given ip to mice once weekly for 24 weeks diacetyl (170 or 840 mgkg [00197 or 00976 mmolkg]) did not induce any lung tumors Acetoin (total doses of 120 or 600 gkg [136 or 681 mmolkg] given ip 3xweek for 6-7 weeks) also showed no carcinogenic activity

Genotoxicity In several bacterial assays diacetyl generally showed mutagenic activity in Salmonella typhimurium strains TA100 102 and 104 with and without metabolic activation but none against strain TA98 Conflicting results were obtained in Escherichia coli strain WP2 uvra but nonmutagenicity was demonstrated in the SOS-chromotest using E coli PQ37 Diacetyl was also negative in a micronucleus test using mouse bone marrow cells It induced sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) AUXB1 cells and unscheduled DNA synthesis in various organs of laboratory animals

Acetoin (up to 4500 mgplate [5108 mmolplate]) was generally nonmutagenic in bacteria in vitro

Cogenotoxicity Diacetyl induced mitotic chromosome loss in Saccharomyces cerevisiae in the presence of propionitrile

Antigenotoxicity In CHO AUXB1 cells bisulfite significantly reduced the frequency of SCEs and proportion of endoreduplicated cells when diacetyl was administered Sodium sulfite and heterocyclic amines inactivated the mutagenicity of diacetyl in S typhimurium strain TA100

Other Data Effects on Enzymes When administered to rats via gastric intubation diacetyl (300 or 1500 mgkg bw [348 or 1742 mmolkg bw]) produced increases in ornithine decarboxylase activity and DNA synthesis in the pyloric mucosa Diacetyl has activating and deactivating effects on several enzymes and metabolic processes including inactivating estradiol 17β-dehydrogenase in human placenta under ultraviolet light In the lysosomal

iv

enzyme α-L-iduronidase it reduced the internalization of the enzyme into human diploid fibroblasts by 50 without affecting enzyme activity and reduced binding to the fibroblast membranes by 90

Possible Mechanism for Lung Damage by Diacetyl Diacetyl may induce lung damage by oxidative stress Lung injury was induced by phosgene and mustard via several processes including free radical generation Lung damage caused by ozone has also been suggested from the formation of reactive free radicals Reduction potentials for diacetyl and its iminium derivatives were found to be in the range favorable for catalytic electron transfer in vivo which can cause oxidative stress via reaction oxygen species as a result of redox cycling

Structure-Activity Relationships Genetic and carcinogenic effects for several diacetyl analogs such as methylglyoxal and acetaldehyde are included in an earlier NTP chemical background document for diacetyl (httpntpniehsnihgovntphtdocsChem_BackgroundExSumPdf431-03-8pdf)

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Table of Contents

Abstract i Executive Summary ii 10 Basis for Nomination1 20 Introduction1

21 Chemical Identification and Analysis 2 22 Physical-Chemical Properties4 23 Commercial Availability4

30 Production Processes5 40 Production and Import Volumes 5 50 Uses 5 60 Environmental Occurrence and Persistence 6 70 Human Exposure6 80 Regulatory Status 8 90 Toxicological Data 9

91 General Toxicology 9 911 Human Data 9 912 Chemical Disposition Metabolism and Toxicokinetics11 913 Acute Exposure12 914 Short-term and Subchronic Exposure16 915 Chronic Exposure16 916 SynergisticAntagonistic Effects 16 917 Cytotoxicity17

92 Reproductive and Teratological Effects17 93 Carcinogenicity 17 94 InitiationPromotion Studies 17 95 Anticarcinogenicity17 96 Genotoxicity 17 97 Cogenotoxicity18 98 Antigenotoxicity 18 99 Immunotoxicity18 910 Other Data18

100 Structure-Activity Relationships 18 110 Online Databases and Secondary References19

111 Online Databases 19 112 Secondary References 20

120 References20 130 References Considered But Not Cited 25 Acknowledgements 26 Appendix A Units and Abbreviations 27 Appendix B Description of Search Strategy and Results 29 Appendix C Volatile Organic Compounds (VOCs) in Popcorn Manufacturing30

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Tables Table 1 Concentrations of VOCs in Microwave Popcorn Manufacturing Plants8 Table 2 Acute Toxicity Values for Some Artificial Butter Flavoring Components12 Table 3 Acute Inhalation Exposure to Artificial Butter Flavoring and Diacetyl 14

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012007 Chemical Information Review Document for Artificial Butter Flavoring

10 Basis for Nomination Artificial butter flavoring and two important constituents diacetyl and acetoin were nominated by the United Food and Commercial Workers International Union (UFCW) for long-term testing via inhalation for respiratory and other toxicity and for cancer-causing properties (httpdefendingscienceorgcase_studiesuploadUnion_petitionto_NTPpdf) After the first incidence of bronchiolitis obliterans associated with microwave popcorn manufacturing in Jasper MO was reported in 2000 several devastating outbreaks of severe and even fatal lung disease including bronchiolitis obliterans have been documented among workers in other microwave popcorn plants who had been exposed to the vapors of butter flavoring These outbreaks have been reported in the scientific literature and the popular press Since butter flavoring mixtures consist of more than 100 different chemicals the most prominent being diacetyl and acetoin the UFCW also recommends that the flavoring mixture as a whole be tested and that the National Toxicology Program (NTP) explore the effects of compounds with chemical and physical properties similar to diacetyl and acetoin

20 Introduction Microwave popcorn is a popular snack food in the United States (US) that is consumed by millions of people in their homes work place and at many types of recreational events It was estimated in 2005 that 156 million bags (39 million pounds) of microwave popcorn are consumed each year in the US (Science News 2005) The consumption of all types of popcorn in 2001 was estimated at one billion pounds per year of which a large portion was microwaveable This is equivalent to ~175 billion quarts per year or an average of ~ 70 quarts per person per year (Food History 2001) In order to keep up with consumer demand in the US alone the microwave popcorn manufacturing industry has to produce over 100 thousand pounds of popcorn per day (assuming a six day work week) One manufacturer alone reported production levels of 150 million bags of microwave and stove-top popcorn in 2006 (Northwest Indiana Times 2006)

Public Health Concern Although there is currently no indication that the general public is at risk of developing lung disease from exposure to vapors released from microwaved popcorn there is growing concern about the risk microwave popcorn producers face Increased incidences of fixed airway obstruction including bronchiolitis obliterans have been recently reported among workers in the microwave popcorn industry Bronchiolitis obliterans is also called popcorn workers lung or popcorn packers lung and is a rare inflammatory disease that affects the small airways Its main respiratory symptoms are cough and shortness of breath the latter may become severe and persistent The first case of bronchiolitis obliterans in a microwave popcorn packaging worker was seen in 1994 but it was the case reports of eight former workers from the same Missouri plant (Gilster-Mary Lee Corporation) with severe bronchiolitis obliterans syndrome that sparked public interest in May 2000 (Kanwal et al 2006b [HETA 2000-0401-2991] Kreiss et al 2002) Several studies suggest that exposure to volatile organic compounds (VOCs) released from butter flavorings used in production processes is the greatest risk factor Two prominent VOCs believed to be the major contributors are diacetyl and acetoin (Kreiss et al 2002) Diacetyl is one of the main components in butter flavoring that gives it its buttery taste and has been identified as a prominent VOC in air samples from microwave popcorn plants (Akpinar-Elci et

1


al 2004 Kanwal 2003 lett [HETA 2002-0089] Kanwal et al 2004 [HETA 2001-0474-2943] 2006a Kanwal and Martin 2003 lett [HETA 2001-0517] Parmet and Von Essen 2002 lett)

Diacetyl is also naturally found in foods and is used as a synthetic flavoring agent and aroma carrier in butter caramel vinegar dairy products and coffee Acetoin is used in the preparation of flavors and essences and found in many of the same foodstuffs as diacetyl (HSDB 2002 2005a) The results from toxicological studies published in the open literature and reported in the Hazardous Substance Database (HSDB) for butter flavoring and two of its primary components diacetyl and acetoin are reviewed here

Diacetyl Acetoin [431-03-8] [513-86-0]

21 Chemical Identification and Analysis Diacetyl (C4H6O2 mol wt = 8609) is also called

23-Butadione 23-Butanedione 23-Diketobutane 23-Dioxobutane Biacetyl Butadiene Butanedione Diacetyl (natural) Dimethyl diketone Dimethyl glyoxal Dimethylglyoxal Glyoxal dimethyl-NSC 8750

Source(s) ChemIDplus 2004a Registry (1984) PubChem CID 650

Acetoin (C4H8O2 mol wt = 8810) is also called

1-Hydroxyethyl methyl ketone 2-Butanone 3-hydroxy-2-Hydroxy-3-butanone 23-Butanolone 3-Hydroxy-2-butanone Acethoin

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Acetoin (natural) Acetyl methyl carbinol Acetylmethylcarbinol Dimethylketol γ-Hydroxy-β-oxobutane Methanol acetylmethyl-NSC 7609

Source(s) ChemIDplus (2004b) HSDB (2005a) PubChem CID 179

Methods that have been used to analyze diacetyl in foodstuffs (eg beer wine butter and butter flavoring) include the National Institute of Occupational Safety and Health (NIOSH) Method 1300 Ketones I use of gas-chromatography (GC) flame ionization detection (FID) with limit of detection (LOD) at 002 mgsample NIOSH Method 1301 Ketones II use of GC-FID with LOD at 005 mgsample and the Association of Official Agricultural Chemists Method 97811 Calorimetric methods are also listed as analytical methods for diacetyl analysis (HSDB 2002) Details of a GC-FID method developed for detecting diacetyl acetoin and other ketones in microwave popcorn manufacturing plants are described in Pendergrass (2004 [PMID14968874]) Sample stability studies using spiked samples collected on Anasorb CMS solid sorbent tubes and stored for seven days at room temperature reported 87-92 (diacetyl) and 63-83 (acetoin) recoveries (Pendergrass 2004 PMID14968874) Recoveries up to 95 were reported for diacetyl samples stored at room temperature for 14 days based on GC-FID analysis (Shah 2006) GC-FID may also be used to identify VOCs including diacetyl in human blood (Houeto et al 2001)

Thermal desorption with GC-mass spectrometry (GCMS) has been used to detect diacetyl acetoin 2-nanonone and other VOCs in butter flavorings and air samples from microwave popcorn manufacturing plants (Kanwal and Kullman 2004 [HETA 2003-0112-2949] Kanwal et al 2004 [HETA 2001-0474-2943] 2006b [HETA 2000-0401-2991] Sahakian et al 2003 [HETA 2002-0408-2915]) A list of VOCs identified in room air and head space samples from butter flavoring mixtures is given in Appendix C Table 1 Headspace volatiles from unsalted sweet butter heated at 100 150 or 200 degC for 5 hours were also collected by simultaneous purging and solvent extraction and are included in the table Analysis by GC-FID nitrogen-phosphorus or flame photometric detectors and GCMS identified 21 aldehydes 12 fatty acids 11 ketones (including diacetyl and 2-nonanone no levels given) 10 nitrogen- andor sulfur-containing compounds 7 alkanes 6 δ-lactones and 4 furans comprising 85 of total volatiles recovered when heated at 200 degC (Lee et al 1991)

Diacetyl in foodstuffs can also be indirectly determined by a differential pulse polarographic method the technique is based on derivatization with o-phenylendiamine to yield quinoxaline (Rodrigues et al 1999 PMID10552634) In wine diacetyl can be determined by solid-phase microextraction followed by GCMS the detection limit ranged from 001 with linearity to 10 microgmL (Hayasaki and Bartowsky 1999 PMID10563940)

Beer samples passed through octadecyl solid-phase extraction column derivatized with 23-diaminonaphthalene and analyzed by high-performance liquid chromatography (HPLC)

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identified diacetyl at 249-353 microgL Analysis of headspace from 26 beer samples showed GC compared to HPLC detected diacetyl at a slightly higher but statistically significant level (McCarthy 1995)

22 Physical-Chemical Properties Property Information Reference(s)

Diacetyl Physical State yellowish-green liquid HSDB (2002) Odor quinone odor chlorine-like odor in HSDB (2002)

vapors rancid butter odor Boiling Point (degC) 88 760 mm Hg HSDB (2002) Melting Point (degC) Flash Point (degC)

-24 72 plusmn 00

HSDB (2002) Registry (1984)

Vapor Pressure (mm Hg) 568 25 degC HSDB (2002) Specific Gravity 0990 15 degC HSDB (2002) Water Solubility 200 gL 15 degC HSDB (2002) Chemical Solubility miscible in alcohol ether soluble in HSDB (2002)

carbitols very soluble in acetone Octanol-water partition coefficient (log P) Bioconcentration Factor (BCF)

-134 10 25 degC and pH 1-10


Acetoin Physical State slightly yellow liquid or crystals HSDB (2005a) Odor buttery HSDB (2005a) Boiling Point (degC) 148 760 mm Hg HSDB (2005a)

143 ChemIDplus (2004b)

Melting Point (degC) 15 HSDB (2005a) Flash Point (degC) 411 HSDB (2005a) Vapor Pressure (mm Hg) Specific Gravity

27 25 degC 09972 gcm3 17degC

HSDB (2005a) HSDB (2005a)

Water Solubility miscible in water HSDB (2005a) Chemical Solubility slightly soluble in alcohol propylene HSDB (2005a)

glycol soluble in acetone ether Octanol-water partition coefficient (log P) -036 HSDB (2005a) Bioconcentration Factor (BCF) 03 HSDB (2005a) Calculated using Advanced Chemistry Development (ACDLabs) Software Solaris V667 [copy1994-2004 ACDLabs]

23 Commercial Availability Butter flavoring is commercially available through the internet from several companies such as Famous Watkins Extracts (best-pricecom 2007) QualityExtractscom (undated) Alibabacom (2007) Syscocom (2006) Country Kitchen SweetArt Inc (undated) and International Flavors and Fragrances Inc (2007) Many of these companies offer both wholesale and retail quantities

Diacetyl is available in technical reagent (lt99) analytical (gt99) and food grades Domestic suppliers found in the Fine Chemicals Database and other sources include Aldrich Chemical Co Alfa Products American Tokyo Kasei Chem Service Inc Crescent Chemical Co Eastman Kodak Co Fischer Chemicals Fluka Chemical Corp ICN Biomedicals Corp International Chemical Group Jansen Chimica Lancaster Synthesis Ltd Mallinckrodt Inc Penta Manufacturing Company Platz amp Bauer Inc Sigma Chemical Co and US Biochemicals Corp The Environmental Protection Agency (EPA) 1983 TSCA Plant and Production (TSCAPP) database reported other industries that manufactured and processed diacetyl include

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Elan Chemical Co Inc Fairmount Chemical Co Inc Union Carbide Co Haarmann amp Reimer Co and Givaudan Co Additional manufacturers and suppliers were found in directories of chemical producers (eg Bell Flavors and Fragrances Inc CA Aromatics Co) and included major companies in Europe the Middle East and Japan (HSDB 2002 NTP 1994)

Companies that produce acetoin include Penta Manufacturing Co and Sigma Aldrich Fine Chemicals (HSDB 2005a) Acros Organics also supplies acetoin (85 wt in water solution and in 93 practical grade) as well as diacetyl (99) (ChemExpercom 2006)

30 Production Processes The use of artificial butter flavorings in microwave popcorn production and the process for preparing the flavoring mixture is described in Section 70

Diacetyl is prepared from methyl ethyl ketone by converting it to an isonitroso compound then hydrolyzing with hydrochloric acid to produce diacetyl It is also produced by oxidation of 2-butanone over a copper catalyst at 300 degC (60 yield) by dehydrogenation of 23-butanediol over a copper or silver catalyst in the presence of air or by acid-catalyzed condensation of 1-hydroxyacetone (obtained by dehydrogenation of 12-propanediol) with formaldehyde Diacetyl is a product of fermentation of glucose via methylacetylcarbinol and of lactic acid bacteria activity during the production of beer (HSDB 2002) Natural diacetyl can be obtained from starter distillate a by-product from the manufacture of dairy starter cultures (webexhibitsorg 2006)

Acetoin is prepared from diacetyl by partial reduction with zinc and acid It is also produced by the action of sorbose bacteria or Mycoderma aceti on 23-butanediol or by the action of fungi such as Aspergillus Penicillium or Mycoderma on sugar cane juice Acetoin is a by-product of fermentation and preparation of cream for churning (HSDB 2005a)

40 Production and Import Volumes The US EPA Inventory Update Rule (IUR) database lists aggregate production volume ranges and companies reporting manufacture for chemicals subject to TSCA IUR reporting requirements In 1986 1990 1994 1998 and 2002 10-500000 pounds of diacetyl production was reported Citrus amp Allied Essences Ltd was listed as a manufacturer for 1998 and Elan Chemical Co for 2002 For acetoin 10-500000 pounds of production was reported in 1994 and 1998 and no production reports were listed for 1986 1990 and 2002 Citrus amp Allied Essences Ltd and Uniroyal Chemcial Co Inc were listed as manufacturers for 1998 (USEPA IUR 2002)

50 Uses Artificial butter flavoring is a popular ingredient for a variety of commercially available food products and for use in home cooking Its found in shortenings and butter flavor alternatives (Bunge Oils Inc 2001 Sweet Celebrations Inc 2003) and some formulations are used as a flavor enhancing additive in the production of a fat-substitute bakery dough (Jewell and Seaman 1994 pat) Numerous product labels including meat marinades such as JohnBoy amp Billys Hot amp Spicy Grillin Sauce (Hot Sauce World undated) low-calorie syrups (Turrisi et al 1985 pat) low-calorie simulated cream cheese (Kong-Chan et al 1991 pat) and emergency food bars (iPreparecom 2006) to name a few list artificial butter flavoring as an ingredient

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Diacetyl is a key flavoring agent and an aroma carrier in butter flavoring butter vinegar coffee and other foods It is used as a synthetic flavoring and adjuvant in oleomargarine candy baked goods ice cream and chewing gum (HSDB 2002) It is also the primary flavor compound in starter cultures and distillates used in producing cultured butter (webexhibitsorg 2006) Diacetyl is used as a chemical modifier of proteins combining with arginine residues It is also used as an electro-stabilizing compound (HSDB 2002) Other uses for diacetyl include reactantstarting material in chemical or biochemical reactions analytical reagent antimicrobialpreservative modifier of radiation response for chemical and biological systems and photoinitiator photosensitizer in polymerizations (NTP 1994)

Acetoin is used as a fragrance carrier and in the preparation of flavors (margarine butter milk yogurt strawberry) and essences (HSDB 2005a)

60 Environmental Occurrence and Persistence Diacetyl is a naturally occurring substance found in some foods It has been reported in butter caramel coffee beer cocoa honey bay and other oils as well as in aroma components of tobacco smoke (Csiba et al 1999 HSDB 2002 OrsquoNeil 2006 Schmalfuss 1950) It was identified in dairy products (eg cheese yogurt milk) by GCMS analysis (Friedrich and Acree undated) and was found in oils of finish pine angelica and lavender as well as in flower specimens of polyalthia canangioides boerl varieties angustifolia and fagroea racemosa jack Other plants reported to contain diacetyl include monodora grandiflora benth magnolia tripetale ximenia aegyptiaca petasites fragrans presl and various narcissi and tulips It is also found in plant volatiles natural aromas of raspberry and strawberry and in oils of lavandin reunion geranium and java citronella (HSDB 2002 OrsquoNeil 2006)

Diacetyl photodegrades quickly in the atmosphere (half-life of ~07 hr) and is not likely to absorb significantly in soil or sediment or to bioconcentrate in fish (HSDB 2002 OrsquoNeil 2006) The photolysis half-life of aqueous-phase diacetyl was 10-16 hr in a study reporting acetic acid peroxyacetic acid and hydrogen peroxide as major and pyruvic acid and methylhydroperoxide as minor photoproducts (Faust et al 1997)

Acetoin is found in butter corn wine vinegar honey cocoa roasted coffee and in currant and strawberry aromas It gradually oxidizes to diacetyl in air and forms a solid dimer on standing or treatment with granulated zinc The dimer is converted back to the monomer by melting distilling or dissolving Acetion has high mobility if released to soil and is not expected to absorb to suspended solids or sediments or to undergo direct photolysis A volatilization half-life of 2 days was reported for a model river and 28 days for a model lake volatilization from dry and moist soil surfaces may also occur Acetion was reported to have low potential for bioconcentration in aquatic organisms (HSDB 2005a OrsquoNeil 2006)

70 Human Exposure One of the primary concerns for human exposure is that of occupational exposure to VOCs from butter flavoring specifically diacetyl and acetoin during the production of microwave popcorn Increased incidences of fixed airway obstruction have been reported in workers from microwave popcorn manufacturing plants The incidence is higher among flavoring mixers packaging

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workers and quality control (QC) personnel During production butter flavoring mixtures are combined with kernel popcorn in microwave bags by the packaging workers The flavoring mixtures are prepared by one to three workers (mixers) per shift in mixing rooms that are often kept at 51-54 degC The mixers measure the butter flavorings (liquid paste or powder form) by hand into open containers (eg 5-gallon buckets) and pour them into 400- to 800-gallon tanks containing heated soybean oil (54-57 degC) Salt and colorings are also poured by hand into these large tanks The mixers may spend 1-15 hoursday on these procedures In some plants the tanks have loose-fitting lids while in others the tanks have no lids When lids must be removed to add ingredients visible clouds of vapors are often released exposing the mixers to volatilized compounds An evaluation of six microwave popcorn plants reported that only one mixer at one plant regularly used a respirator with organic vapor cartridges (Kanwal et al 2006a) The heated flavoring mixture is either piped to the packaging lines where it is combined with kernel popcorn in microwaveable bags or to holding tanks then to the packaging lines In some plants the packaging process is near the large mixing or holding tanks which increases the packaging workersrsquo risk of exposure to volatiles released from the heated oilflavoring mixture increased incidences of obstructive lung disease have been found QC workers who microwave up to 100 bags of popcorn per work shift are also at risk of exposure to oilflavoring vapors that are released when the popped-corn bag is opened Some formulations of powdered butter flavorings that are used do not discharge the flavoring chemicals until the popcorn is heated (Kanwal 2003 lett [HETA 2002-0089] Kanwal et al 2004 [HETA 2001-0474-2943] 2006a) The concentrations (ppm) of five chemicals including diacetyl and acetoin found in air samples taken from different work areas in four microwave popcorn plants are shown in Table 1 A complete list of chemicals identified but not quantified in samples taken from the headspace of butter flavoring mixtures or from room air in manufacturing plants is provided in Appendix C Table I Chemicals in the list that have been tested for pulmonary effects are shown separately in Table II of Appendix C with a brief description of the reported study results

According to the 1989 NIOSH National Occupational Exposure Survey an estimated 3437 workers (1630 females) were exposed to diacetyl (HSDB 2002) Other occupational exposures to diacetyl and many of the alcohols aldehydes esters fatty acids ketones sulfur compounds and hydrocarbons that microwave popcorn workers have been exposed to include the following

bull Production of flavorings (Hansen and Hoffa 2006 lett) bull Manufacturing dairy products or dairy-derived flavoring agents (eg Sunesson et al

2001 [PMID11354733]) bull Food preparation involving cooking with soybean and other seed oils or cooking of meats

(Elmore et al 2001 Schauer et al 1999a Schauer et al 2002a [PMID11883419]) bull Composting biowaste (presumably municipal solid wastesewage) (Tolvanen et al 1998

[PMID15869986]) bull Charcoal production (Greenberg et al 2006) bull Pig farming (Louhelainen et al 2001 PMID11331987) bull Industries involving fermentation with suitable bacteria (eg alcoholic beverage and

bread production [Annemuumlller 1973 Bratovanova 2001] and bull Carpet laying (diacetyl levels in indoor air were 32 microgm3 and 54 microgm3 after four days of

installing latex- or polyurethane-backed carpet respectively) (NTP 1994)

7

Chemical Information Review Document for Artificial Butter Flavoring 012007

Table 1 Air Concentration of Chemicals Identified in Popcorn Manufacturing Plants

Sample Area and Plant Location

Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3

Mixing Area Ridgway IL Nov-2002 06 029 lt0022 019 048 Sioux City IA July-2002 008 lt003 lt002 lt002 0233

Marion OH Mar-2004 126 107 lt005 049 Jasper MO Nov-2000

July-2003 378 046

41 lt0044

55 lt064

037 019

Processing andor Packaging

Ridgway IL Nov-2002 033 018 073 023 042 Sioux City IA July-2002 lt003 003 - 0043

Marion OH Mar-2004 lt003 lt002 lt004 003 - 005 Jasper MO Nov-2000

July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room

Ridgway IL Nov-2002 019 015 019 022 062 Sioux City IA July-2002 ltDL5 0033

Marion OH Mar-2004 lt002 lt002 012 003 Jasper MO Nov-2000

July-2003 054

lt0004 lt0044 lt064 NA

Sources Sahakian et al (2003) [Ridgway IL] Kanwal et al (2004) [Sioux City IA] Kanwal and Kullman (2004) [Marion OH] Kanwal et al (2006b) [Jasper MO] 1 Unless otherwise noted entries are mean concentrations or a range of concentrations reported if the mean was not given concentrations reported in mgm3 were converted to ppm 2 means below the quantifiable values are shown as lt quantifiable value 3 sampled Sept-2003 4

sampled Mar-2002 5 ltDL = below detectable limit

Sources of diacetyl in ambient air to which the general population may be exposed include bull Exhaust emissions from combustion of petroleum-derived fuels in diesel- gasoline- and

jet-fuel-powered engines (Schauer et al 1999b 2002b [PMID11944666] Spicer et al 1992)

bull Fine airborne particulate matter such as that sampled in a California roadway tunnel (Rao et al 2001 PMID11417634)

bull Cigarette smoke (Fujioka and Shibamoto 2006 PMID16463255) bull As a secondary air pollutant resulting from photooxidation of the common gasoline

aromatics toluene xylenes and ethylbenzene and of methyl-substituted aromatic hydrocarbons reacting with nitrogen oxides (NTP 1994)

bull Volatilization of diacetyl-containing aqueous and solid livestock wastes (NTP 1994) bull Moldy buildings (Wilkins et al 1997)

Diacetyl and acetoin are also formed endogenously in humans from decarboxylation of pyruvate (HSDB 2005a)

80 Regulatory Status In the United States diacetyl is regulated by the FDA as a substance directly added to human food it is generally recognized as safe (GRAS) [21 CFR 1841278] (HSDB 2002) Acetoin is also regulated by the FDA as a synthetic flavoring substanceadjuvant for human consumption [21 CFR 18260] and for animal drugs feeds and related products [21 CFR 58260] it is also

8


GRAS (HSDB 2005a) There are no specific occupational exposure limits for diacetyl or acetoin

90 Toxicological Data 91 General Toxicology Toxicology information reviewed here focuses on inhalation studies of butter flavoring VOCs diacetyl and acetoin and their effects on the lungs and respiratory tract Additional toxicological data that were available from reviews (eg an NTP chemical background document [httpntpniehsnihgovntphtdocsChem_BackgroundExSumPdf431-03-8pdf] prepared for the National Cancer Institute in 1994 and profiles from the Hazardous Substances Data Bank [HSDB]) are briefly summarized

911 Human Data In 1994 one case of bronchiolitis obliterans was observed in a packaging worker at a Jasper Missouri microwave popcorn manufacturing plant (Gilster-Mary Lee Corporation) (Kanwal et al 2006b [HETA 2000-0401-2991] Kreiss et al 2002) Additional incidence of bronchiolitis obliterans or obstructive lung disease in other microwave popcorn manufacturing plants including at least three deaths have since been reported (Akpinar-Elci et al 2004 Kanwal 2003 lett [HETA 2002-0089] Kanwal and Martin 2003 lett [HETA 2001-0517] Kreiss et al 2002 Parmet and Von Essen 2002 lett) These include

bull Eight former workers from the Jasper Missouri plant were diagnosed with bronchiolitis obliterans (Kreiss et al 2002 see Kanwal et al 2006b [HETA 2000-0401-2991]) some are candidates for lung transplants o four worked in the butter flavor mixing room and o four worked in the packaging areas

bull Three workers at BK Heuermann Popcorn Inc (Phillips Nebraska) had mildborderline airway obstruction One case was linked to exposure to butter flavorings exposure of the other two cases to butter flavoring mixtures was unknown (Kanwal and Martin 2003 lett [HETA 2001-0517])

bull A butter flavoring mixer at American Pop Corn Company (Sioux City Iowa) was diagnosed with fixed obstructive lung disease consistent with bronchiolitis obliterans (Kanwal et al 2004 [HETA 2001-0474-2943])

bull A butter flavoring mixer at ConAgra Snack Foods (Marion Ohio) was diagnosed with severe fixed obstructive lung disease consistent with bronchiolitis obliterans o 3 of 12 slurry room workers had obstruction of their airways on spirometry and normal

diffusing capacity consistent with bronchiolitis obliterans o 5 packaging area workers had fixed pulmonary obstruction and normal diffusing

capacity o 2 of 11 Quality Assurance workers had abnormal spirometry one had obstruction and

normal diffusing capacity the other had restriction (Kanwal and Kullman 2004 [HETA 2003-0112-2949])

bull At the Agrilink Foods Popcorn Plant (Ridgway Illinois) 10 of 41 workers were suspected of having bronchiolitis obliterans [Note The plants popcorn packaging operations closed January 30 2003] (Sahakian et al 2003 [HETA 2002-0408-2915]

9


Diacetyl was the predominant compound found in the artificial butter flavoring and the room air of the Jasper Missouri plant Workers in the mixing room and packaging area (production areas) were exposed to diacetyl concentrations that were ~800x and 15x respectively the mean concentrations for the office warehouse and outside areas Compared to workers in these areas production area workers had significantly higher rates of shortness of breath on exertion breathing problems a combination of respiratory symptoms unusual fatigue other systemic symptoms and rashes or other skin problems As the cumulative exposure to diacetyl increased the incidence of airway obstruction and abnormal results on spirometry (ie airway obstruction or low forced vital capacity) increased and the average one second forced expiratory volume decreased (Kreiss et al 2002) High-resolution computed tomography (HRCT) showed significant bronchial wall thickening and mosaic shrinking with air trapping Lung biopsies from three fatal cases showed rare granulomas emphysema pneumothoraces andor other symptoms of constrictive bronchiolitis Airways obstruction was not improved in any of the cases by treatment with oral corticosteroids Bronchiolitis obliterans was characterized as having fixed obstruction normal chest radiographs and bronchiectasis and air trapping on HRCT (Akpinar-Elci et al 2004)

Although diacetyl is thought to be the primary contributor to respiratory disease in popcorn manufacturing workers in production areas were also exposed to the highest concentrations of ketones other VOCs and respirable dust (Kreiss et al 2002) Therefore diacetyl may not be the only factor contributing to bronchiolitis obliterans eg tannins have also been proposed as a causal factor (Kreiss et al 2002 Taubert et al 2002 lett)

In a more recent study risk for bronchiolitis obliterans was assessed at six microwave popcorn plants using the Missouri facility as an index plant An eight-hour time-weighted average concentration of diacetyl was used as an indicator of exposure to butter-flavoring VOCs Mixers (those having mixed butter flavorings and oil for at least one day) had higher incidences of all respiratory symptoms (shortness of breath chronic cough and wheezing) compared to those who had never worked in the mixing room mixers having worked gt12 months had higher incidence of all respiratory symptoms and airways obstruction compared to those with less experience Packaging workers in plants where butter flavoring mixing tanks were not adequately separated from the packaging areas also had higher frequencies of all respiratory symptoms and airways obstruction Additionally five of six QC workers in the index plant had airways obstruction and the highest mean diacetyl air concentration (06 ppm) was found in the QC laboratory (Kanwal et al 2006a)

Workers exposed to butter flavoring vapors have also reported eye irritation (chemical burns) skin irritation and nasal irritation (Kanwal 2003 lett [HETA 2002-0089] Kanwal and Martin 2003 lett [HETA 2001-0517]) Patch testing and maximization testing with diacetyl produced no irritation or sensitization respectively in volunteers (NTP 1994) Tests with acetoin also resulted in no irritation or sensitization reactions (Opdyke 1979)

Other industries that have reported incidence of bronchiolitis obliterans in their staff include two workers in a mixing facility of the baking industry (affected within five months of working) workers in flavoring manufacturing plants and a snack food manufacturing worker who was using flavorings and spices (Akpinar-Elci et al 2004 Kreiss et al 2002)

10


912 Chemical Disposition Metabolism and Toxicokinetics The metabolic pathway for diacetyl reduction to acetoin and 23-butanediol is shown below in Figure 1 Results from metabolism studies with rat liver preparations and studies of rats exposed in vivo are summarized following the figure

aO-glu = O-glucuronic acid

CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase

-cleavageoxidation glucuronosyl

transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua

Acetoin 23-butanediolDiacetyl


CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua


Figure 1 Diacetylacetoin metabolism

It is anticipated that humans will metabolize aliphatic acyclic methyl ketones principally by oxidation of the terminal methyl group at low levels of exposure At higher levels reduction to the diol and subsequent conjugation with glucuronic acid is a competing detoxification pathway Other aliphatic acyclic alpha-diketones and alpha-hydroxyketones are reduced conjugated with glucuronic acid and excreted

Diacetyl A single oral dose of diacetyl (430 mgkg bw) was metabolized by reduction to acetoin in male Wistar albino rats Acetoin was found in high concentrations in major organs one hour after dosing 23-Butanediol the reduction product of acetoin was detected in the liver kidney and brain Rat liver homogenate rapidly (10 minute incubation) converted 10 nmol (9 x 10-4 mg) diacetyl to 37 nmol (3 x 10-4 mg) acetoin and 63 nmol (6 x 10-4 mg) butane-23-diol (Otsuka et al 1996)

When administered to male Fischer 344 rats via intragastric gavage a single dose of radiolabeled [14C]-diacetyl (158 158 or 158 mgkg [00184 0184 or 184 mmolkg]) resulted in excretion of 820 727 and 543 of the administered doses respectively as carbon dioxide at 72 hours In urine the excreted amounts were 686 157 and 341 respectively At the high dose elimination via volatile organics in breath and feces was insignificant (maximums of 08 and 225 respectively) In the carcass and tissues 6-7 of the dose was recovered At all tested levels diacetyl was rapidly metabolized and excreted excretion of radioactivity in urine feces and expired breath accounted for 86-87 of the total dose recovered in 24 hours (RTI 1997)

11


In a rat liver preparation diacetyl and ampicillin were formed as metabolites from the hydrolyzation of KB-1585 an ester of ampicillin diacetyl was then metabolized to 23-butanediol via acetoin In normal rat liver mitochondria diacetyl uncoupled oxidative phosphorylation totally eliminated respiratory control with substrates and partially eliminated it with succinate (HSDB 2002) Metabolic interconversions between diacetyl acetoin and 23-butanediol was observed with rat liver extracts (NTP 1994) All three compounds were also acetaldehyde metabolites in perfused liver Diacetyl reduction to acetoin required NADH or NADPH acetoin reduction to 23-butanediol required NADH (Otsuka et al 1996 PMID8882713)

Acetoin Metabolism of acetoin in vivo is mainly by oxidation at low concentrations and by reduction to 23-butanediol at high concentrations In a 24-hour period 1 g of rat liver was estimated to oxidize 86 microg (1 micromol) acetoin In rat and rabbit liver extracts gt95 of radiolabeled [23-14C]-acetoin was detected as a mixture of 23-butanediol stereoisomers When acetoin (doses not provided) was ip injected into albino rats 12C-carbon dioxide was found in expired air (average of 15 during 12 hours) When acetoin was administered orally (3-4 solution) or subcutaneously (20 solution) to rats no diacetyl and very little acetoin were detected in the urine 23-butanediol was the major excretion product (HSDB 2005a) In rabbits orally given acetoin and in rabbit liver homogenate incubated with acetoin (doses not provided) acetylation was increased In male guinea pigs acetoin was an intermediary metabolite in the reduction of methyl ethyl ketone to 23-butanediol (Opdyke 1979)

913 Acute Exposure Acute toxicity values for diacetyl and acetoin are presented in Table 2 Diacetyl was observed to be a severe skin and eye irritant in rabbits (NTP 1994) Acetoin was a moderate irritant on intact and abraded skin of rabbits (Opdyke 1979)

Table 2 Acute Toxicity Values for Some Artificial Butter Flavoring Components

Route Species (sex and strain) LD50LC50 Reference(s)

Diacetyl [431-03-8] inh rat (M F Wistar) 225 lt LC50 lt 52 mgL [4-hr]

(2250 lt LC50 lt 5200 mgm3 639 lt LC50 lt 1477 ppm)

BASF (1993)

ip mouse (sex and strain np) LD50 = 249 mgkg (289 mmolkg) NTP (1994)

rat (sex and strain np) LD50 = 400-650 mgkg (465-755 molkg) ChemIDplus (2004a) NTP (1994)

oral mouse (sex and strain np) LD50 = 250 mgkg (290 mmolkg) NTP (1994)

rat (sex and strain np) LD50 = 1580 mgkg (1835 mmolkg) ChemIDplus (2004a) NTP (1994)

guinea pig (sex and strain np) LD50 = 990 mgkg (1150 mmolkg) ChemIDplus (2004a) NTP (1994)

dermal rabbit (sex and strain np) LD50 gt 5000 mgkg (5808 mmolkg) ChemIDplus (2004a) NTP (1994)

Acetoin [513-86-0]

oral rat (sex and strain np) LD50 gt 5000 mgkg (5675 mmolkg) ChemIDplus (2004b)

dermal rabbit (sex and strain np) LD50 gt 5000 mgkg (5675 mmolkg)

Abbreviations F = female(s) hr = hour(s) inh = inhalation ip = intraperitoneal LC50 = concentration lethal to 50 of test animals LD50 = lethal dose for 50 of test animals M = male(s) np = not provided

12


Details of the following inhalation studies are provided in Table 3

Artificial Butter Flavoring Male rats exposed to vapors from artificial butter flavoring (average diacetyl concentrations 203 285 352 [constant] or 371 [pulsed] ppm range 72-940 ppm) for six hours exhibited necrosis of nasal and airway epithelium At levels of 285-371 ppm diacetyl necrotizing bronchitis was observed in the lung at 203-371 ppm diacetyl necrosuppurative rhinitis and inflammation were seen at all nasal levels (Hubbs et al 2002)

Diacetyl In male C57BL6 mice inhalation of 200 or 400 ppm diacetyl six hours per day for five days caused death and acute necrotizing rhinitis laryngitis and bronchitis (proximal large bronchi) in the 400 ppm group A few deaths and acute necrotizing rhinitis and erosive or necrotizing laryngitis were observed at 200 ppm but lung or bronchiolar lesions were not One hour exposure per day for four weeks (100 200 400 ppm) resulted in chronic bronchitis laryngitis and rhinitis after two and four weeks The response was concentration related ranging from minimal to moderate Two of five mice given 400 mgkg diacetyl by oropharyngeal aspiration died two days after aspiration Foci of fibrosis without inflammation were observed at the junction of the terminal bronchiole and alveolar duct in the three surviving mice Similar lesions with mild inflammation were noted in one of five mice treated with 200 mgkg (Morgan et al 2006 abstr)

Inhalation of diacetyl (99 198 or 295 ppm [349 697 or 1039 mgm3]) for six hours also produced significant necrosis of nasal epithelium at ge198 ppm and significant necrosis of tracheal epithelium at the high dose in male rats No significant effects in the lung were reported (Hubbs et al 2004 abstr)

13


Table 3 Acute Inhalation Exposure to Artificial Butter Flavoring and Diacetyl

Species Strain and Age Number and Sex

of Animals

Chemical Form and Purity

Route Dose Duration and Observation Period

ResultsComments Reference

Artificial Butter Flavoring

Rats Sprague-Dawley Butter flavoring inh (via whole-body Major peaks of vapors (headspace) diacetyl acetic acid butyric Hubbs et al (2002) (Hla[SD]CVF) age np vapors (butter heated exposure chamber) 203 acid acetoin acetoin dimers 2-nonanone and δndashalkyl lactones 19M total (6 4 6 3 to 50 degC for 10 min) 285 352 (constant) or respectively with dose purity NA 371 (pulsed) ppm At the mid-constant and high-pulsed doses one rat each died

[see column 3]) [average diacetyl concentrations] 6 hours necropsied 1 day later

after exposure

Pulmonary findings At the mid and both high doses rats had inflammatory andor necrotizing changes in the airways consisting of multifocal to multifocal and coalescent distribution with moderate to significant severity the main morphologic change was necrotizing bronchitis with decreasing severity of necrosis in smaller airways Constant and pulsed exposures resulted in similar lesions in the mainstem bronchus but necrosis was confined to the mainstem bronchus in constant-exposed rats and to the mainstem bronchus and midsize bronchioles in pulsed-exposed rats Airway and bronchiolocentric changes were increased in mid- and both high-dosed rats compared to controls BAL PMNs were significantly increased in mid- and high-constant rats BAL albumin concentration and macrophage chemiluminescence were significantly increased in both high-dose groups Ultrastructure studies mainly showed necrosis of bronchial epithelium with the mid- and high-constant doses bronchial injury extended beneath the basement membrane and had edema of the lamina propria

Nasal findings Suppurative inflammation and necrosis of the epithelium lining nasal passageways were observed in all exposed rats necrosis sometimes extended beneath epithelial basement membrane Coalescing foci of necrosuppurative rhinitis was seen in respiratory transitional and olfactory epithelium Mid-dose rats had hypercellularity with mostly PMN in the nasal lavage fluid

14


Table 3 Acute Inhalation Exposure to Artificial Butter Flavoring and Diacetyl (Continued)


of Animals




Diacetyl

Rats Sprague-Dawley diacetyl purity np inh (via whole-body Significant effects in the lung were not observed Hubbs et al (2004 age and number np M exposure chamber) 0

993plusmn007 1984plusmn010 or 2946plusmn020 ppm for 6 hours killed the next day

At the mid and high doses rats developed necrosis of nasal epithelium with associated neutrophilic inflammation At the high dose necrosis of tracheal epithelium with associated neutrophilic inflammation was also seen

abstr)

Tracheal changes included the following SEM multifocal denuding of basement membrane with cell swelling loss of microvili and loss of ciliated cells in epithelium

TEM epithelial necrosis denuded basement membrane and elongation of epithelial cells near foci of exposed basement membrane

Rats Wistar (SPF Diacetyl FCC vapor inh (via whole-body At the low dose acute signs included eyelid closure BASF (1993) WistarChbbTHOM) 8- 991 pure exposure chamber) 225 restlessness apathy squatting posture and ruffled furs in all to 9-wk-old 5M and 5F 52 and 239 mgL for 4 rats some animals also showed abdominal and dragging per dose group hours observed for 14

days respiration respiratory sounds and reduced general state By day 5 clinical signs were no longer observed

At the mid and high doses all rats died

Necropsy findings general congestion at the mid and high dose focal hyperemia of the lungs and empty gastrointestinal tract in mid-dose rats focal atelectasis (lobes) and bloody edema of lungs edema and intensified hydrothorax of the bronchi in high-dose rats

Microscopic findings peripheral swelling of liver hepatocytes and moderate emphysema and focal hyperemia in lungs of mid-dose rats extensive hyperemia in lungs necrosis in proximal part of kidney tubulus centrolobular swelling of liver hepatocytes in high-dose rats

225 lt LC50 lt 52 mgL

Abbreviations BAL = bronchoalveolar lavage F = female(s) M = male(s) min = minute(s) NA = not applicable np = not provided PMN = polymorphonuclear leukocyte wk = week(s)

15


In male and female Wistar rats inhalation of diacetyl FCC (225 52 and 239 mgL [6390 1477 or 6788 ppm]) for four hours resulted in deaths at the mid and high doses Necropsy showed general congestion in dead rats focal hyperemia of the lungs and empty gastrointestinal tract in mid-dose animals and atelectasis and bloody edema of the lungs bronchial edema and intensified hydrothorax in high-dose rats Additionally histopathological examination revealed moderate emphysema and focal hyperemia of the lungs as well as peripheral swelling of hepatocytes at the mid dose and widespread hyperemia of the lung necrosis in the proximal tubules of the kidney and centrilobular swelling of hepatocytes at the high dose (BASF 1993)

In in vitro assays diacetyl (1 3 or 10 mM [86 258 or 861 microgmL]) caused contraction and relaxation in perfused guinea pig trachea preparations and damage of the epithelium At the high dose diacetyl completely inhibited responses of the perfused trachea to methacholine but had no effect on reactivity to terbutaline or potassium chloride (Fedan et al 2006)

Acetoin No acute inhalation studies were available

914 Short-term and Subchronic Exposure Diacetyl No short-term or subchronic inhalation studies were available

Daily oral administration of diacetyl (10 30 90 or 540 mgkg [012 035 10 or 627 mmolkg]) for 90 days to rats produced decreased weight gain increased water consumption anemia increased leukocyte count and increased weights of the liver kidney adrenal gland and pituitary gland Necrosis in the stomach was also observed [NOEL = 90 mgkg] (HSDB 2002)

Acetoin No short-term or subchronic inhalation studies were available

When male and female CFE rats were given acetoin (750 3000 or 12000 mgkg [85 330 or 1300 mgkg bwday) in the drinking water for 13 weeks no effects on condition or appearance and no deaths occurred At the high dose male body weights were significantly decreased from week 5 and relative liver weight was statistically significantly increased at weeks 2 6 and 13 females showed these effects after 13 weeks (The effect on the liver may have been due to an increased metabolic load from the high dose) A small but statistically significant decrease in hemoglobin concentration and erythrocyte counts was also observed at the high dose in both sexes Urinalysis blood chemistry and histopathology revealed no other adverse effects [NOEL = 3000 ppm 330 mgkg bwday] (HSDB 2005a)

915 Chronic Exposure No data were available

916 SynergisticAntagonistic Effects When small amounts of 30 acetoin solution (doses not provided) were injected ip into rats to cause loss of righting reflex or respiratory failure blood acetoin concentrations ranged from 227-251 mg percent (average 235 mg) and from 742-770 mg percent (average 754 mg) respectively

16


When ethanol was injected ip into rats alcohol levels ranged from 288-312 mg and 900-952 mg respectively When acetoin and ethanol administration was combined the concentrations of both chemicals in blood were additive (HSDB 2005a)

917 Cytotoxicity Diacetyl (0001 01 or 1 mM [0086 86 or 86 microgmL]) inhibited cell growth in ascites sarcoma cells by 37 at the mid dose and by 100 at the high dose (HSDB 2002)

No data were available for acetoin

92 Reproductive and Teratological Effects When given via oral intubation to pregnant mice for ten days diacetyl (16 g starter distillatekg) had no effects on maternal or fetal survival or nidation There were also no statistically significant changes in the number of fetal abnormalities compared to controls Tests in hamsters and rats gave similar results (HSDB 2002)


93 Carcinogenicity When given ip to mice once weekly for 24 weeks diacetyl (170 or 840 mgkg [00197 or 00976 mmolkg]) did not induce any lung tumors (HSDB 2002 NTP 1994) Acetoin (total doses of 120 or 600 gkg [136 or 681 mmolkg] given ip 3xweek for 6-7 weeks) also showed no carcinogenic activity (Opdyke 1979)

94 InitiationPromotion Studies No data were available

95 Anticarcinogenicity No data were available

96 Genotoxicity Diacetyl In several bacterial assays diacetyl generally showed mutagenic activity in Salmonella typhimurium strains TA100 102 and 104 with and without metabolic activation but none against strain TA98 Conflicting results were obtained in Escherichia coli strain WP2 uvra but nonmutagenicity was demonstrated in the SOS-chromotest using E coli PQ37 Diacetyl was also negative in a micronucleus test using mouse bone marrow cells (CCRIS 1995 NTP 1994) Diacetyl induced sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) AUXB1 cells and unscheduled DNA synthesis in various organs of laboratory animals such as the rat stomach mucosa (HSDB 2002 NTP 1994)

Acetoin Acetoin (up to 4500 mgplate [5108 mmolplate]) was generally nonmutagenic in bacteria in vitro (HSDB 2005a)

17


97 Cogenotoxicity Diacetyl induced mitotic chromosome loss in Saccharomyces cerevisiae only in the presence of propionitrile (NTP 1994)

98 Antigenotoxicity In CHO AUXB1 cells bisulfite significantly reduced the frequency of SCEs and proportion of endoreduplicated cells when diacetyl was administered Sodium sulfite almost completely inactivated the mutagenicity of diacetyl in S typhimurium strain TA100 The reaction of diacetyl with heterocyclic amines also significantly suppressed the mutagenicity in the bacterial strain (NTP 1994)

99 Immunotoxicity Workers exposed to butter flavoring vapors have also reported eye (chemical burns) skin and nasal irritations Patch testing and maximization testing with diacetyl produced no irritation or sensitization respectively in volunteers (NTP 1994) Tests with acetoin also resulted in no irritation or sensitization reaction (Opdyke 1979)

910 Other Data Effects on Enzymes When administered to rats via gastric intubation diacetyl (300 or 1500 mgkg bw [348 or 1742 mmolkg bw]) produced increases in ornithine decarboxylase activity and DNA synthesis in the pyloric mucosa (HSDB 2002 NTP 1994) Diacetyl has activating and deactivating effects on several enzymes and metabolic processes including inactivating estradiol 17β-dehydrogenase in human placenta under ultraviolet light (NTP 1994) Diacetyl reduced the internalization of the lysosomal enzyme α-L-iduronidase into human diploid fibroblasts by 50 without affecting enzyme activity and reduced binding to the fibroblast membranes by 90 a similar reduction was also seen in membranes from rat chondrosarcomas (Rome and Miller 1980)

Possible Mechanism for Lung Damage by Diacetyl Diacetyl may induce lung damage by oxidative stress Reduction potentials for diacetyl and its iminium derivatives were found to be in the range favorable for catalytic electron transfer in vivo which can cause oxidative stress via reaction oxygen species as a result of redox cycling (Kovacic and Cooksy 2005 PMID15654607) In vivo diacetyl may be involved in redox cycling with acetoin and with imino compounds formed by condensation with ammonia or the free amino groups of proteins (Yaylayan et al 2005 PMID16037220) Lung damage caused by ozone has also been suggested to be due to the formation of reactive free radicals (HSDB 2005b)

100 Structure-Activity Relationships Genetic and carcinogenic effects for several analogs such as methylglyoxal and acetaldehyde are included in the background document for diacetyl provided by the NTP (httpntpniehsnihgovntphtdocsChem_BackgroundExSumPdf431-03-8pdf)

18


110 Online Databases and Secondary References 111 Online Databases National Library of Medicine Databases (TOXNET) CCRIS ChemIDplus DART GENETOX HSDB IRIS

STN International Files AGRICOLA IPA BIOSIS MEDLINE BIOTECHNO NIOSHTIC CABA NTIS CANCERLIT Registry EMBASE RTECS ESBIOBASE TOXCENTER

TOXCENTER includes toxicology data from the following files Aneuploidy ANEUPL

BIOSIS Previewsreg (1969-present) BIOSIS

CAplus (1907-present) CAplus International Labour Office CIS

Toxicology Research Projects CRISP

Development and Reproductive Toxicology DARTreg

Environmental Mutagen Information Center File EMIC

Epidemiology Information System EPIDEM

Environmental Teratology Information Center File ETIC

Federal Research in Progress FEDRIP

Health Aspects of Pesticides Abstract Bulletin HAPAB Hazardous Materials Technical Center HMTC

International Pharmaceutical Abstracts (1970-present) IPA

MEDLINE (1951-present) MEDLINE Pesticides Abstracts PESTAB

Poisonous Plants Bibliography PPBIB

Swedish National Chemicals Inspectorate RISKLINE Toxic Substances Control Act Test Submissions TSCATS

These are also in TOXLINE Missing are TOXBIB NIOSHTICreg NTIS

National Archives and Records Administration Code of Federal Regulations (CFR)

In-House Databases Current Contents on Diskettereg

The Merck Index 2006 on CD-ROM

19


112 Secondary References ONeil MJ Ed 2006 The Merck Index 14th ed Merck and Company Inc Whitehouse Station NJ pp 12 and 504

120 References Akpinar-Elci M Travis WD Lynch DA and Kreiss K 2004 Bronchiolitis obliterans syndrome in popcorn production plant workers Eur Respir J 24298-302

Alibabacom 2007 Food flavors (Zhengzhou United Asia Trading Co Ltd China (Mainland)) Internet address httpunitedasiaenalibabacomofferdetail52009934Sell_Food_Flavour_Flavor_Flavouring_Fl avoring_Essencehtml Last accessed on January 17 2007

Annemuumlller G 1973 Formation and decomposition of fermentation by-products in modern processes of discontinuous fermentation and maturing Lebensmittelindustrie 20(10)457-476 Abstract from CAPLUS 197458335

BASF 1993 Study on the acute inhalation toxicity LC50 of Diacetyl FCC as a vapor in rats 4-hour exposure Project No 1310247927010 BASF Aktiengesellschaft Department of Toxicology Ludwigshafen FRG

Best-pricecom 2007 [Search results for butter flavoring] Internet address httpwwwbest-pricecomprocSystemshowProductSearchByUserSearch0butter20flavoringhtml Last accessed on January 25 2007

Bratovanova P 2001 To the issue of formation of acetoin and diacetyl in dough part manufactured products Biotechnol Biotechnol Equip 15(2)124-127 Abstract from CAPLUS 2002109581

Bunge Oils Inc 2004 Nutrition information and ingredient declaration Internet address httpwwwbungefoodscomLiquidButterContenthtm Last accessed on January 25 2007

CCRIS (Chemical Carcinogenesis Research Information System) 1995 23-Butanedione CCRIS Record No 827 Record last revised on March 3 1995 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgov Last accessed on November 13 2006

ChemExpercom 2006 Internet address httpwwwchemexpercom Last accessed on December 18 2006

ChemIDplus 2004a Diacetyl RN 431-03-8 Search at Internet address httpchemsisnlmnihgovchemidplus Last accessed on November 13 2006

ChemIDplus 2004b Acetoin RN 513-86-0 Search at Internet address httpchemsisnlmnihgovchemidplus Last accessed on November 13 2006

Country Kitchen SweetArt Inc Undated [Search results for butter flavoring] Internet address httpwwwcountrykitchensacomcatalogsearchresultsaspxDescription=butter+flavoring Last accessed on January 17 2007

Csiba A Szentgyorgyi M and Lombai G 1999 Identification of health hazardous substances from roasted coffee Elelmezesi Ipar 53(2)37-41 Abstract from CAPLUS 1999243155

20


Elmore JS Mottram SS and Hierro E 2001 Two-fibre solid-phase microextraction combined with gas chromatography-mass spectrometry for the analysis of volatile aroma compounds in cooked pork J Chromatogr A 905(1-2)233-240 Abstract from CAPLUS 2000891101

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Acknowledgements Support to the National Toxicology Program for the preparation of Chemical Information Review Document for Artificial Butter Flavoring was provided by Integrated Laboratory Systems Inc through NIEHS Contract Number N01-ES-35515 Contributors included Scott A Masten PhD (Project Officer NIEHS) and from ILS Inc Marcus A Jackson BA (Principal Investigator) Bonnie L Carson MS Claudine A Gregorio MA Yvonne H Straley BS Pamela Y MaGee BS and Sherry D Blue AA

26


Appendix A Units and Abbreviations ordmC = degrees Celsius microgL = microgram(s) per liter microgm3 = microgram(s) per cubic meter microgmL = microgram(s) per milliliter microM = micromolar bw = body weight CCRIS = Chemical Carcinogenesis Research Information System CHO = Chinese hamster ovary DNA = deoxyribonucleic acid EPA = Environmental Protection Agency F = female(s) FDA = Food and Drug Administration FID = flame ionization detection g = gram(s) gkg = gram(s) per kilogram gmL = gram(s) per milliliter GC = gas chromatography GRAS = generally recognized as safe hr = hour(s) HRCT = high-resolution computed tomography HSDB = Hazardous Substances Data Bank ip = intraperitoneal(ly) kg = kilogram(s) lb = pound(s) LC = liquid chromatography LC50 = lethal concentration for 50 of test animals LD50 = lethal dose for 50 of test animals LOD = limit of detection M = male(s) mgkg = milligram(s) per kilogram mgL = milligram(s) per liter mgm3 = milligram(s) per cubic meter mgmL = milligram(s) per milliliter mm = millimeter(s) mM = millimolar mmol = millimole(s) mmolkg = millimoles per kilogram MMWR = Morbidity and Mortality Weekly Report mol = mole(s) mol wt = molecular weight NIOSH = National Institute for Occupational Safety and Health NOEL = no observable effect level np = not provided NTP = National Toxicology Program OSHA = Occupational Safety and Health Administration

27


PEL = permissible exposure limit ppm = parts per million QC = quality control SCE = sister chromatid exchange TSCA = Toxic Substances Control Act TSCAPP = TSCA Plant and Production UFCW = United Food and Commercial Workers VOC = volatile organic compound wk = week(s)

28


Appendix B Description of Search Strategy and Results

An initial search of the usual biomedical databases (MEDLINE CABA AGRICOLA EMBASE BIOTECHNO ESBIOBASE BIOSIS IPA and TOXCENTER) was conducted using only the CAS Registry Numbers to represent numerous compounds found in butter or butter flavoring Keywords for the concepts lung injury cancer and association with flavoring butter margarine or popcorn were combined with the aggregate answer number for the compounds A later search for diacetyl and acetoin was restricted to CAPLUS Their CAS numbers were combined with concepts for adverse effects industrial hygiene or occurrence in the environment

Brief searches for certain other butter flavoring volatiles or other compounds found in room air at two facilities were done in Google Scholar PubMed and the TOXNET databases especially ChemIDplus HSDB and TOXLINE These compounds searched were generally aldehydes carboxylic acids and others suspected of having possible lung toxicity because of their chemically reactive nature Searches were also done to identify VOCs from heated soybean oil heated butter and heated popcorn kernels in the absence of added flavoring Heated butter is of interest because natural butter flavorings would be expected to have many more volatiles than just the few compounds selected for manufacturing artificial flavors Searches confirmed that hydrogen sulfide is reported by several references to be a major volatile from microwave popping of unflavored popcorn kernels or other heating of corn but no original source was found to confirm that hydrogen sulfide exposure may lead to bronchiolitis obliterans as stated by Boswell and McCunney (1995)

29


Appendix C Volatile Organic Compounds (VOCs) in Popcorn Manufacturing

Table I VOCs identified in head space samples from butter flavoring mixtures andor air samples from three microwave popcorn plants a

Chemical Name CASRN PubChem

CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d

Ridgway (Liq or Paste)

QC Room

Ridgway e

Mixing Room

Ridgway e Sioux City f

(Liq or Paste)

Sioux City (Powder)

Jasper g

Major Constituents Identified in Butter Flavoring and Found in Room Air

Diacetyl 23-Butanedione h 431-03-8 650 x 100 Major Major Major Major Minor Major

Acetic acid 64-19-7 176 x Major Major Major Major Minor Major

2-Butanone Methyl ethyl ketone 78-93-3 6569 x Major Major Major Major Major Major

Ethanol 64-17-5 702 x Major Major Major Major Major NL

Limonene dl-Limonene Dipentene (R)-(+)-Limonene d-Limonene (S)-(-)-Limonene l-Limonene

138-86-3 5989-27-5 5989-54-8

22311 440917 439250

100 Major Major Major Major Major Major

(QC room)

Butyric acid 107-92-6 264 100 Major Major Minor Major Minor NL

Ethyl butyrate 105-54-5 7929 x Major Major Major Minor Minor NL

Ethyl acetate [with 2-ethyl-2-methyloxirane for Ridgway] 141-78-6 8857 Major Major Major Minor NL

Acetonitrile 75-05-8 6342 Major Major Major Minor NL

Decane 124-18-5 15600 x 150 Major Major Major Minor NL

3-Methylacetoin 3-Hydroxy-3-methyl-2-butanone 115-22-0 8261 Major Minor Minor Minor Minor NL

Acetoin 3-Hydroxy-2-butanone 513-86-0 179 x Major Major Major NL NL NL

2-Nonanone Methyl n-heptyl ketone 821-55-6 13187 x Major Major Major NL NL Major

Dimethyl sulfide Methyl sulfide 75-18-3 1068 Major Major Major NL NL NL

δ-Decalactone 5-Decalactone 705-86-2 12810 x Major Major NL NL NL

δ-Dodecalactone 713-95-1 12844 x 150 Major Minor NL NL NL NL

Hexanedione 23-Hexanedione 34-Hexanedione

3848-24-6 4437-51-8

19707 62539

x Major Minor Minor NL NL NL

11-Diethoxyethane Acetal 105-57-7 7765 Major Minor Minor NL NL NL

2-Heptanone Methyl amyl ketone MAK 110-43-0 8051 x 100 Major Minor Minor NL NL NL

Isobutanal Isobutyraldehyde 78-84-2 6561 x 100 Major Minor Minor NL NL NL

Acetaldehyde 75-07-0 177 Major NL NL Major Minor NL

Ethyl lactate Ethyl 2-hydroxypropionate 97-64-3 637513 Major NL NL Minor Minor NL

Propanoic acid Propionic acid 79-09-4 1032 x Major NL NL Minor NL

30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g

Minor Constituents Identified in Butter Flavoring and Found in Room Air

Dodecane 112-40-3 8182 x Minor Major Major Minor Minor NL

Tridecane 629-50-5 12388 x Minor Minor Major Minor Major NL

Silicone compounds (decamethylcyclopentasiloxane polydimethylsiloxane and Dow corning 345) [possible artifacts from analytical method or from anti-foam agents used with flavorings eg polydimethylsiloxane)

541-02-6 10913 Minor Major Major Major Major

Hexamethylcyclotrisiloxane 541-05-9 10914 Minor Minor Minor Minor Minor NL

Methyl propionic acid ester [esters of isobutyric acid methyl propanoate isoamyl 2-methylbutyl and phenethyl isobutyrates]

554-12-1 11124 Minor Minor Minor Minor Minor NL

Methanol 67-56-1 887 Minor Major Major NL NL NL

δ-Undecalactone 710-04-3 61204 150 Minor Major Minor NL NL NL

Formaldehyde 50-00-0 712 Minor NL NL NL

Pentanal Valeraldehyde 110-62-3 8063 x 100 Minor NL NL Minor NL

Constituents Identified in Butter Flavoring but NOT Room Air

11-Diethoxybutane Butyraldehyde diethyl acetal 3658-95-5 77225 Major NL NL NL NL NL

2-Methyl-13-dioxolane 497-26-7 10342 Major NL NL NL NL NL

Hexanoic acid Caproic acid 142-62-1 8892 x 100 Major NL NL NL NL NL

Aliphatic estersoxygen compounds (Some were identified separately in room air samples)

NA NA Major NL NL NL NL NL

Acetylpyridine 2-Acetylpyridine 3-Acetylpyridine 4-Acetylpyridine

30440-88-1 350-03-8

1122-54-9

14286 9589

14282 x Major NL NL NL NL NL

Alkyldioxolanes NA NA Major NL NL NL NL NL

Butyl isobutyrate 97-87-0 7353 Major NL NL NL NL NL

C18H14O4 isomers Dihydroxydimethylhexanedione NA NA Major NL NL NL NL NL

Decanoic acid Capric acid 334-48-5 2969 150 Major NL NL NL NL NL

Ethyl decanoate Ethyl caprate 110-38-3 8048 x Major NL NL NL NL NL

Ethyl hexanoate Ethyl caproate 123-66-0 31265 Major NL NL NL NL NL

Ethyl octanoate Ethyl caprylate 106-32-1 7799 Major NL NL NL NL NL

31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g

Ethyl propionate 105-37-3 7749 Major NL NL NL NL NL

Ethyl vinyl ether Vinamar 109-92-2 8023 Major NL NL NL NL NL

1-Hydroxy-2-butanone 2-Oxobutanol 5077-67-8 521300 x Major NL NL NL NL NL

Methyl hexanoate Methyl caproate 106-70-7 7824 Major NL NL NL NL NL

Methylpentenal (2-methyl-2-pentenal) 623-36-9 5319754 Major NL NL NL NL NL

γ-Nonalactone Coconut aldehyde 104-61-0 7710 x Major NL NL NL NL NL

γ-Decalactone 706-14-9 12813 Minor NL NL NL NL NL

Dodecanoic acid Lauric acid 143-07-7 3893 x 100 Major NL NL NL NL NL

Ethyl dodecanoate Ethyl laurate 106-33-2 7800 Minor NL NL NL NL NL

Propanal Propionaldehyde 123-38-6 527 Major NL NL NL NL NL

Vanillin 4-Hydroxy-3-methoxybenzaldehyde 121-33-5 1183 x Minor NL NL NL NL NL

Dimethyl sulfoxide DMSO Methyl sulfoxide 67-68-5 679 Major NL NL NL NL NL

Isobornyl isovalerate Isobornyl isopentanoate 7779-73-9 No CID Major NL NL NL NL NL

Maltol [also a soybean volatile] NA NA 200 Major NL NL NL NL NL

Nitrogen compounds NA NA Minor NL NL NL NL NL

n-Pentanoic acid Valeric acid 109-52-4 7991 x 150 NL NL NL NL NL

n-Pentanol Amyl alcohol 71-41-0 6276 x NL NL NL NL NL

Xylene - o-Xylene - m-Xylene - p-Xylene

[Peaks for butter flavoring are either not well separated from butyric acid or are ltlt005 See EthylbenzeneXylenes]

95-47-6 108-38-3 106-42-3

7237 7929


Chemicals Identified in Room Air but NOT Butter Flavoring

Isopropyl alcohol 2-Propanol Isopropanol 67-63-0 3776 NL Major Major Major Major NL

Propane 74-98-6 6334 NL Major Major Major Major NL

Tetradecane [peaks not numbered for Ridgway chromatograms]

629-59-4 12389 x NL Major Major Minor Minor NL

Acetone 2-Propanone 67-64-1 180 NL Major Major Minor NL

Furfural 2-Furaldehyde 2-Hydroxymethylfuran 98-01-1 7362 x 150 NL Minor (w octane)

Major Major NL

Hexane 110-54-3 8058 100 NL Major Major NL

32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g

2-Ethyl-2-methyloxirane 12-Epoxy-2-methylbutane (2-R- epimer) (2-S- epimer) [+ ethyl acetate in Ridgway room air]

30095-63-7 7830021 7832547

NL Major Major NL NL NL

Octamethylcyclotetrasiloxane 556-67-2 11169 NL NL NL NL

Octanone 2-Octanone 3-Octanone

111-13-7 106-68-3

8093 246728

150 NL NL NL Minor NL

Octanal 124-13-0 454 x 150 NL Minor Minor Major NL

β-Pinene 127-91-3 14896 NL NL NL Minor Minor NL

Benzene [with Isopropyl acetate] 71-43-2 241 NL NL NL Major Minor NL

ButaneButene 106-97-8 7843 NL Major Major NL NL NL

Butyl Cellosolve Ethylene glycol monobutyl ether 111-76-2 8133 NL Minor Minor Minor Major NL

C8 aliphatic hydrocarbons NA NA NL Major Minor Minor Minor NL

C9-C16 mostly branched alkanes and aliphatic hydrocarbons plus some C9-C10 alkylbenzenes

NA NA NL Major Major Minor Minor NL

p-Dichlorobenzene 106-46-7 4685 NL Major Minor NL

22-Dimethoxybutane Butyraldehyde dimethyl acetal 3453-99-4 137941 NL Minor Major NL NL NL

Isooctane 26635-64-3 11594 NL Minor Minor Major Minor NL

1-Methoxy-2-propanol Propylene glycol monomethyl ether

107-98-2 7900 NL Major Major Major Minor NL

3-Methyl-3-buten-2-one isopropenyl methyl ketone 814-78-8 13143 NL Minor Minor Major Minor NL

α-Methylstyrene (methylstyrene isomer) 98-83-9 7407 NL Major Minor Minor NL

Nonane 111-84-2 8141 x 100 NL Major Major Major Minor NL

Aliphatic oxygen compounds (methoxybutene) two compounds not have numerous NLM database records 2-methylbutanal (96-17-3) and 3-methylbutanal (isovaleraldehyde 590-86-0)

NA NA NL Minor Major NL NL NL

Bromoethane Ethyl bromide 74-96-4 6332 NL Major NL NL NL

3-Buten-2-one Methyl vinyl ketone 78-94-4 6570 NL Minor Major Minor Minor NL

C5H10 isomers NA NA NL NL NL Major Minor NL

C6 aliphatic hydrocarbons NA NA NL NL NL Major Major NL

NN-Dimethylformamide 68-12-2 6228 NL Minor Major NL NL NL

33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g

Dimethylstyrene p α-Dimethylstyrene 1195-32-0 62385 NL NL NL Minor Major NL

Heptanal Heptaldehyde 111-71-7 8130 100 NL NL NL Major Minor NL

Isopentane 78-78-4 6556 NL NL NL Major Major NL

Octane 111-65-9 356 100 NL Major Minor NL NL NL

Heptane 142-82-5 8900 100 NL Minor Minor Minor Minor NL

Naphthalene 91-20-3 931 x NL Minor Minor Minor Minor NL

Propylene glycol methyl ether acetate PGMEA 108-65-6 7946 NL Minor Minor Minor Minor NL

111-Trichloroethane Methyl chloroform 71-53-6 6278 NL Minor Minor Minor NL

2-Butenal Crotonaldehyde [(E)-Crotonaldehyde (123-73-9) same PubChem]

4170-30-3 447466 NL Minor Minor NL NL NL

Butyl acrylate 141-32-2 8846 NL NL NL Minor Minor NL

tert-Butyl peroxide Di-tert-butyl peroxide 110-05-4 8033 NL Minor Minor NL NL NL

Butyronitrile 109-74-0 8008 NL NL NL Minor Minor NL

C7 aliphatic hydrocarbons NA NA NL NL NL Minor Minor NL

Chloromethane Methyl chloride 74-87-3 6327 NL NL NL NL

Formic acid 64-18-6 284 NL NL NL Minor Minor NL

Nitromethane Carbon disulfide 112-Trichloro-122-trifluoroethane (CFC 113)

75-52-5 75-15-0 76-13-1

6375 6348 6428

NL Minor Minor NL NL NL

2-Propoxyethanol Ethylene glycol monopropyl ether 2807-30-9 17756 NL NL NL Minor Minor NL

Trichlorofluoromethane CFC-11 75-69-4 6389 NL NL NL Minor NL

Chemicals Identified in Room Air and Questionable in Butter Flavoring

Perchloroethylene 1122-Tetrachloroethene 127-18-4 31373 Major NL NL Major Major NL

Methylene chloride Dichloromethane 75-09-2 6344 Major NL NL Minor Minor NL

Pentane [not well separated from diacetyl peak in butter flavor]

109-66-0 8003 100 Major Major Minor Major Major NL

Hexanal [also a soy volatile] 66-25-1 6184 x 100 Major Minor Minor Minor Major NL

Undecane 1120-21-4 14257 100 Minor Minor Major Major Major NL

Toluene 108-88-3 1140 x Minor Major Major Major Major NL

Ethylbenzene 100-41-4 7500 Minor Major Minor Major Major NL

Nonanal 124-19-6 31289 x 100 Minor Minor Minor Major Major NL

34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g

α-Pinene [peaks not numbered for Ridgway chromatograms]

80-56-8 6654 Minor Minor Major Major NL

Diethyl phthalate 84-66-2 6781 Minor Major Minor Minor Minor NL

Dimethyl phthalate 131-11-3 8554 Minor Major Minor NL NL NL

C7-C10 aliphatic aldehydes [Straight-chain aldehydes octanal nonanal and decanal are listed separately]

NA NA Minor Minor Minor NL NL NL

Decanal 112-31-2 8175 x 100 Minor NL NL Minor Minor NL

Sometimes present in media andor system blanks

May be present as a thermal decomposition product andor impurity of ethanol

a Relative level of VOCs estimated from thermal desorption chromatograms based on peak height as reported by Kanwal et al (2004) [Sioux City IA HHE] Sahakian et al (2003) [Ridgway IL HHE] and Gomaa et al (2001) [Jasper MO HEE] included in Kanwal et al (2006) [HHE p 92] Bold Italics (column 1) = Some respiratory effects data available and summarized in Table II below Major = major constituent based on relative peak height Minor = minor constituent based on relative peak height Major = possible major constituent (not labeled on chromatogram) based on peak location compared to analyte list Minor = possible minor constituent (not labeled on chromatogram) based on peak location compared to analyte list = shown on analyte list but no peak was visible on chromatogram NL = not labeled on chromatogram or on analyte list and NA = not applicable

b Identified in VOCs from microwave popped popcorn without oil or butter flavoring (Buttery et al 1997 Rengarajan and Seitz 2004)

c Fresh sweet butter (as opposed to rancid butter which has a higher concentration of butyric acid) temperature (Celsius) to which butter was heated (5 hours) to produce VOCs (Lee et al 1991)

d Ridgway facility Bulk butter flavoring (liquid or paste) was heated to 50 ˚C and headspace samples analyzed (Nov 2002) the range of peak heights on the chromatogram was lt05 to 95 x 106 the cut-off between major and minor peaks was set at 3 x 106 (visible point of separation) Some peak numbers on chromatograms were slightly out of order and occasionally more unlabeled peaks were seen between those that were labeled than expected based on the corresponding analyte list (eg four peaks between peak 70 and 74)

e Room air the range of peak heights was lt01 to 19 x 106 The cut-off between major and minor peaks was 03 x 106 (visible point of separation)

f Sioux City facility Mixing room air the range of peak heights was lt005 x 106 to gt095 x 106 The cut-off between major and minor was 015 x 106 (visible point of separation)

g Jasper facility Room air from all areas of the facility unless otherwise noted the range of peak heights was lt 02 to gt3 x 106 The chemical identities for only a few peaks were shown on the chromatogram (no list of analytes available) and all of them were considered major

h Levels of diacetyl were much lower when butter was heated to gt150 ˚C (appears to decompose) Thermal decomposition of diacetyl gave methane carbon monoxide ketene (CH2=C=O) and ketene polymers among other products possibly via a free-radical mechanism (Rice and Walters 1939) Ketene is as acutely toxic to the lungs as phosgene (Wooster et al 1946)

35


Table II Brief respiratory effects data for compounds identified in butter flavoring volatiles andor room air of popcorn plants

Compound (CAS amp PubChem No) Potential for Nasal and Lung Toxicity

Acetaldehyde (75-07-0 CID 177) Upper respiratory tract at the high concentration inhalation exposure increased nasal tumors in rats and laryngeal and nasal tumors in hamsters 52-week exposure at concentrations up to 1500-3000 ppm caused labored breathing degeneration of olfactory epithelium hyper- and metaplastic changes in respiratory epithelium and rhinitis in rats Mucous membrane irritation and ciliastatic effects may occur in the upper respiratory tract of humans at gt100-200 ppm (HSDB 230 2005)

Lungs Lung tumors were not induced by intratracheal dosing of hamsters but ldquoperibronchiolar ademomatoid lesionsrdquo were observed in the lung Ciliotoxic and mucus coagulating effects were seen At the end of a 5-week study rats inhaling 243 ppm showed increased functional residual capacity residual volume total lung capacity and respiratory frequency Damage to the peripheral regions of the lung parenchyma affected small airways or altered pulmonary elastic properties (HSDB 230 2005) Acetaldehyde may cause oxidative DNA damage in rat lung tissues (Xi et al 2004) It may induce bronchoconstriction in human asthmatics when inhaled (Sanchez-Toril et al 2000)

Acetic acid (64-19-7 CID 176) Several persons acutely exposed to high concentrations after a glacial (100) acetic acid spill developed reactive airways dysfunction syndrome (RADS) (Kern 1991) High acute exposure in rats failed to induce RADS (Ariel et al 1998)

Acetonitrile (75-05-8 CID 6342) Vapors are irritating to eyes nose and throat Massive exposures induce respiratory asphyxiation due to cyanide poisoning Rats inhaling the LC50 or LC84 developed pulmonary edema (HSDB 42 2005) In a 2-year study in rats and mice equivocal evidence of hepatic tumors but no lung toxicity was reported In a 13-week study no clear histopathological effects were observed but some rats died early with pulmonary congestion and edema and hemorrhage in the lung and brain (NTP TR-447 1996)

Bromoethane Ethyl bromide (74-96-4 CID 6332)

Respiratory irritant Only highest dose (400 ppm) in 2-year carcinogenesis bioassay induced nasal and alveolar epithelial hyperplasia (HSDB 532 2005)

2-Butenal Crotonaldehyde (4170-30-3 CID 447466) [(E)-Crotonaldehyde (123-73-9)]

A strong respiratory irritant causing pulmonary edema at high concentrations (HSDB 252 2005)

3-Buten-2-one Methyl vinyl ketone (78-94-4 CID 6570)

Twelve inhalation exposures over 12 days caused upper airway irritation and necrosis in mice and rats rats were more sensitive (Morgan et al [NTP] 2000)

Butyl acrylate (141-32-2 CID 8846) Acrylate esters (hydrolyzed in nasal and lung tissues to acrylic acid) and acrylic acid itself induced olfactory epithelial lesions in rodents respiratory epithelium was ldquorelatively unaffectedrdquo Esters induced glutathione (GSH) and nonprotein GSH depletion (Miller et al 1981a 1981b Stott and McKenna 1985 Vodicka et al 1990)

Butyl Cellosolve Ethylene glycol monobutyl ether EGBE 2-Butoxyethanol (111-76-2 CID 8133)

Pulmonary edema was reported in acute oral poisoning of an alcoholic man (Bauer et al 1992) In a 2-year inhalation study in mice and rats hyaline degeneration of the olfactory epithelium was induced there were no effects on the lungs (NTP TR-484 2000)

tert-Butyl peroxide Di-tert-butyl peroxide (110-05-4 CID 8033)

Low acute inhalation as well as dermal and eye toxicity (BIBRA 1990)

Butyric acid (107-92-6 CID 264) Butyric acid and Na butyrate were included in a structure-activity model of compounds with documented ability to induce respiratory sensitization (Graham et al 1997) Butyric acid octanoic acid and other small fatty acids induced maternal respiratory toxicity in rats gavaged on gestation days 6-15 (Narotsky et al 1991 1994) Severe lung changes were observed in rabbits after inhalation of aerosol (40 mgL = 40000 mgm3) for 15 hours (Danishevskii and Monastyrskaya 1960)

Butyric acid may have a pathophysiological role in some tumors and obstructive lung diseases or upper respiratory tract cancers In in vitro studies with cell lines from human nasopharyngeal carcinomas Na butyrate upregulated expression of IL-6 and IL-2R Elevated serum IL-6 has been associated with several human cancers including lung cancer and chronic lung diseases including bronchiolitis obliterans after lung transplantation (Chow et al 2003 Lu et al 2002 Wang et al 1999)

Butyronitrile (109-74-0 CID 8008) REL=22 mgm3 Symptoms of human exposure to nitriles include bronchial tightness and respiratory distress (NIOSH 1978)

36



Chloromethane Methyl chloride (74-87-3 CID 6327)

May be corrosive at high concentrations producing pulmonary edema with lesions and disturbing surfactant metabolism (Huguenard et al 1975) The mortality incidence of 24 persons accidentally exposed to methyl chloride 32 years previously showed increased risk ratios for cardiovascular disease and all cancers including lung (Rafnsson and Gudmundsson 1997) Induced more severe and extensive necrosis of the olfactory epithelium in rats than in mice in a 6-week inhalation study and damaged several organs (Eustis et al [NTP] 1988)

Decanal (112-31-2 CID 8175) Low-molecular-weight aldehydes are irritating to the membranes of the nasal and oral passages and the upper respiratory tract inducing bronchial constriction choking and coughing (HSDB 288 2002)

Longer-chain aldehydes and carboxylic acids might be expected to be less irritating than the lower-chain members based on observations that nasal pungency (irritation) declined in the homologous series of aldehydes (butanal through octanal) and carboxylic acids (formic butyric hexanoic and octanoic) in volunteer anosmics (Cometto-Muniz et al 1998)

p-Dichlorobenzene (106-46-7 CID 4685) One of 11 common VOCs found in human blood (US population in the third NHANES study in 1988-1994) that was still associated with reduced pulmonary function after adjustment for smoking (Elliott et al 2006) Also one of the most common VOCs found in indoor air and in exhaled human breath (eg Wallace et al 1991)

NN-Dimethylformamide (68-12-2 CID 6228)

No involvement of the respiratory tract in the toxicity (HSDB 78 2005)

Dimethyl sulfide Methyl sulfide (75-18-3 CID 1068)

No reports of lung toxicity were found however a worker exposed to high concentrations in a confined space died of hypoxia (Terazawa et al 1991) Vapor is moderate eye nose and throat irritant (HSDB 356 2002) The 24-hour LC50 in rats (4 hour exposure) was 40250 ppm (Tansy et al 1981)

Ethylbenzene (100-41-4 CID 7500)Xylenes o-Xylene (95-47-6 CID 7237) m-Xylene (108-38-3 CID 7929) p-Xylene (106-42-3 CID 16821)

In a 2-year bioassay in rats and mice 750 ppm induced alveolar epithelium metaplasia alveolarbronchiolar adenoma and liver toxicity in male mice and liver tumors in female mice (Chan et al [NTP] 1998 NTP TR-466 1999)

Ethyl vinyl ether Vinamar (109-92-2 CID 8023)

Probably not a respiratory tract irritant 4-hour LC50 in rats was gt21200 mgm3 15-minute LC50 in mice was 324000 mgm3

(ChemIDplus 2004) Formaldehyde (50-00-0 CID 712) Induced nasal squamous cell carcinomas in rats and mice but not lung lesions in a 2-year cancer bioassay (Kerns et al [CIIT] 1983)

Strength of evidence for nasopharyngealsino-nasal cancer = strong pulmonary edema = good allergic asthma = good and laryngeal and lung cancer = limited (CHE undated)

Formic acid (64-18-6 CID 284) A 13-week inhalation study in rats and mice reported squamous metaplasia and degeneration in olfactory and respiratory epithelia (NTP TOX-19 1992)

Furfural 2-Furaldehyde 2-Hydroxymethylfuran (98-01-1 CID 7362)

Human respiratory irritant 13 week inhalation exposure of guinea pigs and 4 week exposure of rats induced nasal histopathology Induced pulmonary irritation parenchymal injury and regenerative proliferation of type II pneumocytes in a 30-day rat inhalation study (HSDB 542 2006)

Hexanal (66-25-1 CID 6184) Inhalation of 2 or 10 ppm did not affect pulmonary function but did cause eye and nose discomfort and headaches in humans (Ernstgard et al 2006)

Hexanoic acid Caproic acid (142-62-1 CID 8892)

Mild to strong skin eye and respiratory tract irritant No inhalation studies were available (BUA 2005 Canadian Centre for Occupational Health and Safety 1990 HSDB 6813 2006)

37



Hydrogen sulfide (7783-06-4 CID 402) Mentioned in the literature as having induced bronchiolitis obliterans (eg Boswell and McCunney 1995) but only one original [not listed in Table I requires use of a published report was found Two patients had RADS and one had chemical pneumonitis with bronchiolitis obliterans and fibrosis The specific analytical method to detect] latter case did not improve with treatment (Malbrain et al 1997) Four years after poisoning by inhalation a patient who had suffered

pulmonary edema developed pulmonary fibrosis (Duong et al 2001) Several community-based epidemiological studies (one in South Sioux City NB) noted increased incidences of respiratory diseases in communities with compared to those without H2S emission sources (eg Bates et al 1998 Campagna et al 2004 Durand and Wilson 2006 Legator et al 2001)

High concentrations induced nasal lesions in rodents and anosmia and dysosmia in humans (Brenneman et al [CIIT] 2002) Concentrations up to 80 ppm for ge90 days caused nasal (olfactory neuronal loss) and lung toxicity in rats and mice Rats developed bronchiolar epithelial hypertrophy and hyperplasia (Dorman et al [CIIT] 2004)

Note Levels of hydrogen sulfide and -butyrolactone emitted from popping unflavored popcorn were 1000-fold higher than levels of most other compounds emitted Special methods were needed to trap and quantify H2S (Buttery et al 1997)

Isobutanal Isobutyraldehyde (78-84-2 CID 6561)

Eye and respiratory tract irritant Inhalation of high doses induced fatal pulmonary edema in animals (HSDB 614 2003) Exposure to ge1000 ppm for up to 105 weeks induced severe nonneoplastic nasal lesions abnormal respiratory sounds andor slowed respiration without lung lesions in rats and mice (Abdo et al 1998 NTP TR-472 1999)

Ketene Ethenone (463-51-4 CID 10038) Acute toxicity values in several species may be found in the IDLH documentation Death was from pulmonary edema (NIOSH 1996) [not listed in Table I but it is a thermal Acute inhalation toxicity is comparable to that of phosgene and hydrogen cyanide (Wooster et al 1946) Repeated exposures may lead decomposition product of diacetyl] to tolerance delayed toxicity resembles that of phosgene-emphysema and fibrosis (HSDB 633 2005)

Note Ketene (CH2=C=O) and ketene polymers are among the thermal decomposition products of diacetyl (Rice and Walters 1939) appears that diacetyl in sweet butter decomposes when heated above 150 ˚C diacetyl levels are lower than those at 100 ˚C (Lee et al 1991) A NIOSH or OSHA colorimetric method recommended for ketene analysis was not used in the health hazard evaluations of the microwave popcorn plants (ie OSHA CSI sampling method [SKC Inc 2007] or NIOSH 2S92 [OSHA 1992 Sigma-Aldrich Co 1999)

Limonene dl-Limonene Dipentene (138-86-3 CID 22311) (R)-(+)-Limonene d-Limonene (5989-27-5 CID 440917) (S)-(-)-Limonene l-Limonene (5989-54-8 CID 439250)

Exposure to 450 mgm3 (~81 ppm) for 2 hours caused decreased vital capacity in exercising human volunteers (Falk-Filipsson et al 1993) The sensory irritation threshold is gt80 ppm for humans and gt100 ppm for mice Mice showed mild broncho-constriction after short exposures to either enantiomer at gt1000 ppm (Larsen et al 2000)

d-Limonene is readily oxidized by ozone and its oxidation products cause significant upper airway irritation at concentrations well below NOELs of the unoxidized form (Wolkoff et al 2000) Mice exposed to ozone-limonene reaction products (original limonene concentration 51 ppm [~280 mgm3]) showed both upper airway irritation and ldquoairflow limitation that persisted for at least 45 min post exposurerdquo (Rohr et al 2002)

1-Methoxy-2-propanol Propylene glycol monomethyl ether PGME (107-98-2 CID 7900)

No lung toxicity was observed in rats or mice in a 2-year cancer bioassay (Spencer et al 2002) or in rats inhaling vapors in a 2-generation reproductive study (Carney et al 1999)

3-Methyl-3-buten-2-one Isopropenyl methyl ketone (814-78-8 CID 13143)

Eyes nose and throat irritant rats guinea pigs and rabbits given 20 or 100 seven-hour inhalation exposures to 30 ppm or 15 ppm respectively had ocular and nasal irritation and kidney damage (HSDB 1164 2002)

Methylene chloride Dichloromethane (75-09-2 CID 6344)

Inhalation produced alveolarbronchiolar neoplasms and hepatocellular neoplasms in mice Rat tumors did not involve the lungs [NTP bioassay] (HSDB 66 2005)

Methylstyrene isomer α-Methylstyrene (98-83-9 CID 7407)

Toxicity in rodents inhaling high concentrations for 9-12 days did not involve the lungs (Morgan et al [NTP] 1999)

Naphthalene (91-20-3 CID 931) Rat inhalation induced nasal and lung tumors [NTP bioassay] (Abdo et al 2001) Nitromethane (75-52-5)Carbon disulfide112-Trichloro-122-trifluoroethane (CFC 113)

Nitromethane is an eye and respiratory irritant it is neurotoxic and carcinogenic (HSDB 106 2006) Carbon disulfidersquos toxicity does not involve the respiratory tract (HSDB 52 2005)

38



Octanal (124-13-0 CID 454) Low-molecular-weight aldehydes are irritating to the membranes of the nasal and oral passages and the upper respiratory tract inducing bronchial constriction choking and coughing (HSDB 5147 2003)

Perchloroethylene 1122-Tetrachloroethene (127-18-4 CID 31373)

Occupational asthma reported in humans acutely exposed to high concentrations (Boulet 1988)

Propanal Propionaldehyde (123-38-6 CID 527)

Mice guinea pigs and rabbits that inhaled high concentrations developed fatal pulmonary edema (HSDB 1193 2003)

Propanoic acid Propionic acid (79-09-4 CID 1032)

No inhalation toxicity studies were found but one case of mild cough and asthmatic response was reported corrosive caused severe eye and skin burns and was irritating to the eyes skin and lungs (HSDB 1192 2006)

Propylene glycol methyl ether acetate PGMEA (108-65-6 CID 7946)

Short-term inhalation study (300-3000 ppm) in rats showed no lung toxicity (PGMEA is rapidly hydrolyzed to PGME and acetic acid) (Miller et al 1984)

2-Propoxyethanol Ethylene glycol monopropyl ether (2807-30-9 CID 17756)

Rabbits tolerated 2400 ppm 1-3 hours exhibiting only irritation of the mucous membranes Rats inhaling an atmosphere saturated with ethylene glycol monopropyl ether for 7 hours showed lung liver and kidney injuries Twelve 8-hour inhalation exposures to 600 ppm had no effect on mice and guinea pigs but were lethal to cats and rabbits No lung toxicity in pregnant rats that inhaled 100-400 ppm for 6 hours on gestation days 6-15 (HSDB 6499 2002)

Tetradecane (629-59-4 CID 12389) Lung injury appeared to be mediated by disruption of airway barrier epithelial function (Robledo et al 2000) and inflammatory mechanisms (Harris et al 1997 Wang et al 2001) Inhalation of jet propulsion fuel 8 vapors (contains n-tetradecane) for 7 or 28 days increased pulmonary resistance in rats but no pathological evidence of lung injury (Pfaff et al 1995)

111-Trichloroethane Methyl chloroform (71-55-6 CID 6278)

Inhalation for up to 90 days produced almost no toxicity in several species (HSDB 157 2005)

Undecane (1120-21-4 CID 14257) Rats inhaling each of the alkanes n-nonane to n-tridecane showed cerebellar and liver toxicity but not lung toxicity (Nilsen et al 1988)

Sometimes present in media andor system blanks NHANES = National Health and Nutrition Examination Survey

References

Abdo KM Haseman JK and Nyska A 1998 Isobutyraldehyde administered by inhalation (whole body exposure) for up to thirteen weeks or two years was a respiratory tract toxicant but was not carcinogenic in F344N rats and B6C3F1 mice Toxicol Sci 422)135-151 Abstract from PubMed 9579026

Abdo KM Grumbein S Chou BJ and Herbert R 2001 Toxicity and carcinogenicity study in F344 rats following 2 years of whole-body exposure to naphthalene vapors Inhal Toxicol 13(10)931-950 Abstract from PubMed 11696867

Ariel AP Furlott HG Chapman KR Slutsky AS Webster P Zamel N and Tarlo SM 1998 Effect of high dose inhaled acetic acid on airway responsiveness in fischer rats Can Respir J 5(5)349-354 Abstract from PubMed 9832602

Bates MN Garrett N Graham B and Read D 1998 Cancer incidence morbidity and geothermal air pollution in Rotorua New Zealand Int J Epidemiol 27(1)10-14 Abstract from PubMed 9563687

Bauer P Weber M Mur JM Protois JC Bollaert PE Condi A Larcan A and Lambert H 1992 Transient non-cardiogenic pulmonary edema following massive ingestion of ethylene glycol butyl ether Intensive Care Med 18(4)250-251 Abstract from PubMed 1430593

39


BIBRA (The British Industrial Biological Research Association) 1990 Di-tert-butyl Peroxide Toxicity Profile The British Industrial Biological Research Association Carshalton UK 4 pp Abstract from TOXLINE (Secondary Source ID RISKLINE1990050006 entered in May 1990) Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenTOXLINE Last accessed on January 9 2007

Boswell RT and McCunney RJ 1995 Bronchiolitis obliterans from exposure to incinerator fly ash J Occup Environ Med 37(7)850-855 Abstract from PubMed 7552470

Boulet LP 1988 Increases in airway responsiveness following acute exposure to respiratory irritants Reactive airway dysfunction syndrome or occupational asthma Chest 94(3)476-481 Abstract from PubMed 2842114

Brenneman KA Meleason DF Sar M Marshall MW James RA Gross EA Martin JT and Dorman DC 2002 Olfactory mucosal necrosis in male CD rats following acute inhalation exposure to hydrogen sulfide Reversibility and the possible role of regional metabolism Toxicol Pathol 30(2)200-208 Abstract from PubMed 11950163

BUA (Beratergremium fuumlr umweltrelevante Altstoffe) 2005 Caproic acid BUA Vol 241 89 pp Abstract from TOXCENTER 2004151446

Buttery RG Ling LC and Stern DJ 1997 Studies on popcorn aroma and flavor volatiles J Agric Food Chem 45(3)837-843

Campagna D Kathman SJ Pierson R Inserra SG Phifer BL Middleton DC Zarus GM and White MC 2004 Ambient hydrogen sulfide total reduced sulfur and hospital visits for respiratory diseases in northeast Nebraska 1998-2000 J Expo Anal Environ Epidemiol 14(2)180-187 Abstract from PubMed 1501549

Canadian Centre for Occupational Health Safety 1990 Chemical information sheet Hexanoic acid Canadian Centre for Occupational Health Safety 1 p Abstract from TOXCENTER 2002513983

Carney EW Crissman JW Liberacki AB Clements CM and Breslin WJ 1999 Assessment of adult and neonatal reproductive parameters in Sprague-Dawley rats exposed to propylene glycol monomethyl ether vapors for two generations Toxicol Sci 50(2)249-258 Abstract from PubMed 10478862

Chan PC Hasemani JK Mahleri J and Aranyi C 1998 Tumor induction in f344n rats and b6c3f1 mice following inhalation exposure to ethylbenzene Toxicol Lett 99(1)23-32

CHE (The Collaborative on Health and the Environment) Undated CHE Toxicant and Disease Database Displaying diseases linked to formaldehyde (grouped by strength of evidence) Internet address httpdatabasehealthandenvironmentorgindexcfm Last accessed on January 24 2007

ChemIDplus 2004 Vinamar RN 109-92-2 Search at Internet address httpchemsisnlmnihgovchemidplus Last accessed on December 20 2006

Chow KC Chiou SH Ho SP Tsai MH Chen CL Wang LS and Chi KH 2003 The elevated serum interleukin-6 correlates with the increased serum butyrate level in patients with nasopharyngeal carcinoma Oncol Rep 10(4)813-819

Cometto-Muniz JE Cain WS and Abraham MH 1998 Nasal pungency and odor of homologous aldehydes and carboxylic acids Exp Brain

40


Res 118(2)180-188 Abstract from PubMed 9580061

Danishevskii SL and Monastyrskaya BI 1960 Toxicity of butyric acid (Russ) Tr Leningr Sanit Gigien Med Inst 6278-84 Abstract from TOXCENTER 196216996

Dorman DC Struve MF Gross EA and Brenneman KA 2004 Respiratory tract toxicity of inhaled hydrogen sulfide in Fischer-344 rats Sprague-Dawley rats and B6C3F1 mice following subchronic (90-day) exposure Toxicol Appl Pharmacol 198(1)29-39 Abstract from PubMed 15207646

Duong TX Suruda AJ and Maier LA 2001 Interstitial fibrosis following hydrogen sulfide exposure Am J Ind Med 40(2)221-224 Abstract from PubMed 11494351

Durand M and Wilson JG 2006 Spatial analysis of respiratory disease on an urbanized geothermal field Environ Res 101(2)238-245 Abstract from PubMed 16169550

Elliott L Longnecker MP Kissling GE and London SJ 2006 Volatile organic compounds and pulmonary function in the third national health and nutrition examination survey 1988-1994 Environ Health Perspect 114(8)1210-1214

Ernstgard L Iregren A Sjogren B Svedberg U and Johanson G 2006 Acute effects of exposure to hexanal vapors in humans J Occup Environ Med 48(6)573-580 Abstract from PubMed 16766921

Eustis SL Haber SB Drew RT and Yang RS 1988 Toxicology and pathology of methyl bromide in F344 rats and B6C3F1 mice following repeated inhalation exposure Fundam Appl Toxicol 11(4)594-610 Abstract from PubMed 3229585

Falk-Filipsson A Lof A Hagberg M Hjelm EW and Wang Z 1993 d-Limonene exposure to humans by inhalation Uptake distribution elimination and effects on the pulmonary function J Toxicol Environ Health 38(1)77-88 Abstract from PubMed 8421324

Gomaa A Kullman G Fedan K ENLight P Schleiff P Phillips PE Simoes E and Kreiss K 2001 Appendix C NIOSH Investigation of Gilster-Mary Lee Corporation HETA 2000-0401 Technical Assistance to Missouri Department of Health Interim Report August 22 2001 Cited by Kanwal et al (2006)

Graham C Rosenkranz HS and Karol MH 1997 Structure-activity model of chemicals that cause human respiratory sensitization Regul Toxicol Pharmacol 26(3)296-306 Abstract from EMBASE 1998031306

Harris DT Sakiestewa D Robledo RF and Witten M 1997 Immunotoxicological effects of JP-8 jet fuel exposure Toxicol Ind Health 13(1)43-55 Abstract from PubMed 9098949

HSDB (Hazardous Substances Data Bank) 2002 Decaldehyde HSDB No 288 Record last updated on November 8 2002 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 24 2007

HSDB 2002 Dimethyl sulfide HSDB No 356 Record last revised on November 8 2002 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on December 5 2006

41


HSDB 2002 Methyl isopropenyl ketone HSDB No 1164 Record last updated on November 16 2002 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 24 2007

HSDB 2002 Ethylene glycol monopropyl ether HSDB No 6499 Record last updated on May 13 2002 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 24 2007

HSDB (Hazardous Substances Database) 2003 Isobutyraldehyde HSDB No 614 Record last revised on January 24 2003 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 11 2007

HSDB 2003 Propionaldehyde HSDB No 1193 Record last updated on February 14 2003 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 24 2007

HSDB 2003 Octylaldehyde HSDB No 5147 Record last updated on January 24 2003 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 24 2007

HSDB 2005 Acetonitrile HSDB No 42 Record last revised on June 24 2005 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on December 5 2006

HSDB 2005 Carbon Disulfide HSDB No52 Record last revised on June 24 2005 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 11 2007

HSDB 2005 Dichloromethane HSDB No 66 Record last updated on June 24 2005 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 24 2007

HSDB 2005 NN-Dimethylformamide HSDB No 78 Record last revised on June 24 2005 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 9 2007

HSDB 2005 111-Trichloroethane HSDB No 157 Record last revised on June 24 2005 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 26 2007

HSDB 2005 Acetaldehyde HSDB No 230 Record last revised on June 24 2005 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 23 2007

HSDB 2005 Crotonaldehyde (2-Butenal) HSDB No252 Record last revised on June 24 2005 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 8 2007

HSDB 2005 Ethyl Bromide HSDB No532 Record last revised on June 24 2005 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 9 2007

HSDB 2005 Ketene HSDB No 633 Record last revised on June 24 2005 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 8 2007

HSDB 2006 Nitromethane HSDB No 106 Record last revised on April 14 2006 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 9 2007

42


HSDB 2006 Furfural HSDB No 542 Record last updated on August 30 2006 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 24 2007

HSDB 2006 Propionic acid HSDB No 1192 Record last updated on December 20 2006 Internet address (available via TOXNET on NLM) httptoxnetnlmnihgovcgi-binsishtmlgenHSDB Last accessed on January 24 2007

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44


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45


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46

Abstract

Artificial butter flavoring and two important constituents diacetyl and acetoin were nominated by the United Food and Commercial Workers International Union for long-term testing via inhalation for respiratory and other toxicity and for cancer-causing properties There is growing concern that workers in the microwave popcorn manufacturing industry may be at risk of developing the lung disease bronchiolitis obliterans from exposure to vapors from artificial butter flavoring The first case of bronchiolitis obliterans in a popcorn manufacturing worker was reported in 2000 in Missouri Since then several devastating outbreaks of severe and even fatal lung disease including bronchiolitis obliterans have been documented among workers in microwave popcorn manufacturing plants who have been exposed to the vapors of butter flavoring To date limited toxicological studies are available for artificial butter flavoring and its constituents Inhalation studies in male rats showed that exposure to vapors from artificial butter flavoring caused necrosis of nasal and airway epithelium Necrotizing bronchitis was observed in the lung and necrosuppurative rhinitis and inflammation were seen at all nasal levels An inhalation study with diacetyl also produced significant necrosis of nasal epithelium and significant necrosis of tracheal epithelium in male rats However no significant effects in the lung were reported In another inhalation study necropsy revealed general congestion focal hyperemia of the lungs atelectasis and bloody edema of the lungs bronchial edema and intensified hydrothorax in rats that did not survive a four hour treatment with diacetyl Histopathological examination showed emphysema hyperemia of the lungs peripheral or centrilobular swelling of hepatocytes and necrosis in the proximal tubules of the kidney In rats [14C]-diacetyl given by intragastric gavage was rapidly metabolized and excreted primarily as carbon dioxide in the breath and in urine Metabolism of acetoin in vivo was mainly by oxidation at low concentrations and by reduction to 23-butanediol at higher concentrations Diacetyl was not a reproductive or teratological toxicant in studies with pregnant mice rats or hamsters Intraperitoneal injections of diacetyl or acetoin did not induce tumors in mice Diacetyl but not acetoin was mutagenic in some strains of bacteria It was negative in a micronucleus test but induced sister chromatid exchanges in Chinese hamster ovary AUXB1 cells and unscheduled DNA synthesis in various organs of laboratory animals Diacetyl exhibited activating and deactivating effects on several enzymes and metabolic processes It has been postulated that oxidative stress may play a role in diacetyl-induced lung damage

i

Executive Summary




ii










iii












iv




v

Table of Contents









vi


vii





1










2








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46

Executive Summary




ii










iii












iv




v

Table of Contents









vi


vii





1










2








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46










iii












iv




v

Table of Contents









vi


vii





1










2








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46












iv




v

Table of Contents









vi


vii





1










2








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46




v

Table of Contents









vi


vii





1










2








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46

Table of Contents









vi


vii





1










2








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46


vii





1










2








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46





1










2








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46










2








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46








3






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46






-24 72 plusmn 00




-134 10 25 degC and pH 1-10





27 25 degC 09972 gcm3 17degC






4









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46









5








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46








6










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46










7




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46




Sample Date

Diacetyl1

ppm Acetoin

ppm Acetaldehyde

ppm

Acetic Acid ppm

Respirable Dust

mgm3



July-2003 378 046

41 lt0044

55 lt064

037 019




July-2003 169

lt0004 lt0044 27

lt064 013 003

QC Room



July-2003 054

lt0004 lt0044 lt064 NA











8













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46













9







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46







10




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46




CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO H3C

CH3O

O-glua



CH3

OO

H3C CH3

OO

H3C

acetoin

reductase

H3C

CH3

OH

OH

H3C

CH3

OH

OH

H2 O+CO2 H2 O+CO2

H3C

CH3

O-glua

OH

H3C

CH3

O-glua

OH

H3C

CH3

OH

O

H3C

CH3

OH

O

glucuronosyl

transferase

diacetyl

reductase


transferase

CO2 +

CH3O

OHO

CO2 +

CH3O

OHO

CH3O

OHO H3C

CH3O

O-gluaH3C

CH3O

O-glua






11









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46









BASF (1993)







Acetoin [513-86-0]




12






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46






13




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46




of Animals







after exposure



14




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46




of Animals




Diacetyl




abstr)










15











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46











16












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46












17








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46








18






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46






















19
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46
















20















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46















21















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46















22
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46
















23

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46

















24
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46
















25








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46








26



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46



27



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46



28





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46





29





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46





CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g







138-86-3 5989-27-5 5989-54-8

22311 440917 439250


(QC room)













3848-24-6 4437-51-8

19707 62539








30



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















30440-88-1 350-03-8

1122-54-9

14286 9589









31



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g




















95-47-6 108-38-3 106-42-3

7237 7929









Major Major NL


32



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


30095-63-7 7830021 7832547




111-13-7 106-68-3

8093 246728

























33



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















75-52-5 75-15-0 76-13-1

6375 6348 6428














34



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46



CID

Dry b

popcorn

Sweet c

Butter at (˚C)

Butter Flavor d


QC Room

Ridgway e

Mixing Room


(Liq or Paste)

Sioux City (Powder)

Jasper g


















35






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46






















36
























37
























38



















References






39
















40
















41

















42
















43














44















45













46
























37
























38



















References






39
















40
















41

















42
















43














44















45













46
























38



















References






39
















40
















41

















42
















43














44















45













46



















References






39
















40
















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44















45













46
















40
















41

















42
















43














44















45













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46

Documents

Artificial Butter Flavoring